The conscious perception of thermal stimuli is divided into two categories: thermal sensation (i.e., discriminative component) and pleasantness/unpleasantness (i.e., hedonic component). There have been very few studies which clearly dissociated the two components. The aim of the present study was 1) to identify brain regions involved in perception of thermal stimuli per se, dissociating those related to the two components, and additionally 2) to examine brain regions of the explicit evaluation processes for the two components. Sixteen participants received local thermal stimuli of either 41.5 °C or 18.0 °C during whole-body thermal stimuli of 47.0 °C, 32.0 °C, or 17.0 °C. The local stimuli were delivered to the right forearm with the Peltier device. The whole-body stimuli delivered through a water-perfusion suit was aimed to modulate thermal pleasantness/unpleasantness to the local stimulus. The local stimulation at the same temperature was conducted five times with 30-s intervals. Brain activation was assessed by functional magnetic resonance imaging (fMRI), and the participants were asked to report their ratings of thermal sensation and pleasantness/unpleasantness following the cessation of each local stimulus. Local thermal stimulation activated specific brain regions such as the anterior cingulate cortex, insula, and inferior parietal lobe, irrespective of the temperature of local and whole-body stimuli; however, no specific activation for hot or cold sensation was observed. Different brain regions were associated with pleasantness and unpleasantness; the caudate nucleus and frontal regions for pleasantness, and the medial frontal and anterior cingulate cortex for unpleasantness. In addition, the explicit evaluation process for the discriminative and hedonic components immediately following the cessation of local stimulus involved different brain regions; the medial prefrontal cortex extending to the anterior cingulate cortex, insula, middle frontal cortex, and parietal lobes during the explicit evaluation of thermal sensation, and the medial prefrontal cortex, posterior cingulate cortex, and inferior parietal lobes during that of pleasantness/unpleasantness.

The aim of the present study was to clarify physical risks during hot-water bathing by measuring thermal and cardiovascular responses and thermal sensation. Young men and women (n = 7 and 5, respectively) participated in the present study, which consisted of two trials mimicking bathing behavior at room temperature of 25 °C and 15 °C. Participants bathed in 41 °C water for 20 min to the subclavian level. Before bathing, participants rested fully clothed for 15 min and then rested for 15 min without clothes. After bathing, they rested without clothes for 15 min and afterwards rested fully clothed for another 15 min. Tympanic temperature (Tty), heart rates (HR), mean skin temperature (Tsk), mean arterial pressure (MAP), and laser-Doppler flow at the chest and forehead (LDFhead and LDFchest) were evaluated. Thermal perception was assessed with a visual analogue scale. Mean Tsk in the 15 °C trial decreased during the period without clothing while MAP increased. The value remained unchanged in the 25 °C trial. During bathing, Tty, mean Tsk, HR, LDFhead, and LDFchest increased in both trials, and MAP decreased to similar levels. Relative change in LDFchest was greater in the 15 °C trial than in the 25 °C trial. Participants felt cold when they were without clothes at 15 °C; however, the thermal perception during bathing was similar between the two trials. Greater changes in cardiovascular and thermal responses were observed during the bathing behavior. In addition, bathing in cold room augmented the changes, which may induce some physical risks during bathing.

Fasted rats place their tails underneath their body trunks in the cold (tail-hiding behavior), which is a thermoregulatory behavior. The aim of the present study was to investigate the effect of fasting and des-acyl ghrelin, a hormone related to fasting, on tail-hiding behavior and neural activity in the cold. Wistar rats were divided into 'fed', '42-h fasting' and des-acyl ghrelin groups. The rats received an intraperitoneal saline or 30-μg des-acyl ghrelin injection, and were then exposed to 27 °C or 15 °C for 2-h with continuous body temperature (Tb), tail skin temperature (Ttail), and tail-hiding behavior measurements. cFos immunoreactive (cFos-IR) cells in the insula, secondary somatosensory cortex, medial preoptic nucleus, parastrial nucleus, amygdala, and lateral parabrachial nucleus were counted in four segments: seg1, 2, 3, and 4 (bregma -0.36, -1.44, -2.64, and -9.00 mm), respectively. At 15 °C, Tb and Ttail were lower in the 42-h fasting group than in the fed and des-acyl ghrelin groups, and the duration of tail-hiding behavior was longer in the 42-h fasting and des-acyl ghrelin groups than in the fed group. The onset of tail-hiding behavior more advanced in the des-acyl ghrelin group than in the fed group at 15 °C. Only at the insula in seg3 at 15 °C, the number of cFos-IR cells was greater in the 42-h fasting group than in the fed group. Both the 42-h fasting and des-acyl ghrelin groups might modulate the tail-hiding behavior of rats in a cold, and a part of the insula might be involved this response during fasting.

cFos expression in the preoptic area (PO), which is thermoregulatory center increased by both heat and cold exposures; however, the regional difference is unknown yet. We aimed to determine if cFos expression in the PO was regionally different between heat and cold exposures. Mice were exposed to 27, 10, or 38°C for 90min, and body temperature (Tb) was measured. cFos-immunoreactive (cFos-IR) cells in the PO were counted by separating the PO into the ventral and dorsal parts in the rostral (bregma 0.38mm), central (-0.10mm), and caudal (-0.46mm) planes. Tb at 10°C remained unchanged; however, it increased at 38°C. Counts of cFos-IR cells in all areas were greater at 38°C than at 27°C. In the dorsal and ventral parts of the central and the dorsal part of caudal PO, counts of cFos-IR cells were greater at 10°C than at 27°C. In conclusion, the areas of increased cFos expression in the PO in the heat were different that in the cold in mice.

The processes of thermoregulation are roughly divided into two categories: autonomic and behavioral. Behavioral thermoregulation alone does not have the capacity to regulate core temperature, as autonomic thermoregulation. However, behavioral thermoregulation is often utilized to maintain core temperature in a normal environment and is critical for surviving extreme environments. Thermal comfort, i.e., the hedonic component of thermal perception, is believed to be important for initiating and/or activating behavioral thermoregulation. However, the mechanisms involved are not fully understood. Thermal comfort is usually obtained when thermal stimuli to the skin restore core temperature to a regulated level. Conversely, thermal discomfort is produced when thermal stimuli result in deviations of core temperature away from a regulated level. Regional differences in the thermal sensitivity of the skin, hypohydration, and adaptation of the skin may affect thermal perception. Thermal comfort and discomfort seem to be determined by brain mechanisms, not by peripheral mechanisms such as thermal sensing by the skin. The insular and cingulate cortices may play a role in assessing thermal comfort and discomfort. In addition, brain sites involved in decision making may trigger behavioral responses to environmental changes.

We evaluated cold sensation at rest and in response to exercise-induced changes in core and skin temperatures in cold-sensitive exercise trained females. Fifty-eight trained young females were screened by a questionnaire, selecting cold-sensitive (Cold-sensitive, n = 7) and non-cold-sensitive (Control, n = 7) individuals. Participants rested in a room at 29.5°C for ~100 min after which ambient temperature was reduced to 23.5°C where they remained resting for 60 min. Participants then performed 30-min of moderate intensity cycling (50% peak oxygen uptake) followed by a 60-min recovery. Core and mean skin temperatures and cold sensation over the whole-body and extremities (fingers and toes) were assessed throughout. Resting core temperature was lower in the Cold-sensitive relative to Control group (36.4 ± 0.3 vs. 36.7 ± 0.2°C). Core temperature increased to similar levels at end-exercise (~37.2°C) and gradually returned to near preexercise rest levels at the end of recovery (>36.6°C). Whole-body cold sensation was greater in the Cold-sensitive relative to Control group during resting at a room temperature of 23.5°C only without a difference in mean skin temperature between groups. In contrast, cold sensation of the extremities was greater in the Cold-sensitive group prior to, during and following exercise albeit this was not paralleled by differences in mean extremity skin temperature. We show that young trained females who are sensitive to cold exhibit augmented whole-body cold sensation during rest under temperate ambient conditions. However, this response is diminished during and following exercise. In contrast, cold sensation of extremities is augmented during resting that persists during and following exercise.

Rats place their tails underneath their bodies in the cold (tail-hiding behavior), which is a behavioral indicator of thermoregulation. The aim of the present study was to elucidate the effect of estradiol (E2) on tail-hiding behavior and neural activity assessed by immunohistochemistry. Ovariectomized rats were implanted with a silastic tube with or without E2 underneath the dorsal skin (E2(-) and E2(+) groups), and exposed to 27°C, 16°C, and 10°C for 2h with continuous body temperature (Tb), tail skin temperature (Ttail), and behavioral measurements. cFos immunoreactive (cFos-IR) cells in the insula, secondary somatosensory cortex, medial preoptic nucleus, parastrial nucleus, amygdala, and lateral parabrachial nucleus were counted. Tb and Ttail were not different between the E2(-) and E2(+) groups. At 16°C, the duration and the onset of tail-hiding behavior in the E2(+) group were greater than that in the E2(-) group. The number of cFos-IR cells in the insula of the E2(-) group was greater than that of the E2(+) group in rats kept at 16°C. E2 might modulate tail-hiding behavior of female rats at 16°C, and the insula may be involved in the response.

BACKGROUND: The aims of this study were to (1) evaluate whether recently introduced methods of measuring axillary temperature are reliable, (2) examine if individuals know their baseline body temperature based on an actual measurement, and (3) assess the factors affecting axillary temperature and reevaluate the meaning of the axillary temperature. METHODS: Subjects were healthy young men and women (n = 76 and n = 65, respectively). Three measurements were obtained: (1) axillary temperature using a digital thermometer in a predictive mode requiring 10 s (T ax-10 s), (2) axillary temperature using a digital thermometer in a standard mode requiring 10 min (T ax-10 min), and (3) tympanic membrane temperature continuously measured by infrared thermometry (T ty). The subjects answered questions about eating and exercise habits, sleep and menstrual cycles, and thermoregulation and reported what they believed their regular body temperature to be (T reg). RESULTS: T reg, T ax-10 s, T ax-10 min, and T ty were 36.2 ± 0.4, 36.4 ± 0.5, 36.5 ± 0.4, and 36.8 ± 0.3 °C (mean ± SD), respectively. There were correlations between T ty and T ax-10 min, T ty and T ax-10 s, and T ax-10 min and T ax-10 s (r = .62, r = .46, and r = .59, respectively, P < .001), but not between T reg and T ax-10 s (r = .11, P = .20). A lower T ax-10 s was associated with smaller body mass indices and irregular menstrual cycles. CONCLUSIONS: Modern devices for measuring axillary temperature may have changed the range of body temperature that is recognized as normal. Core body temperature variations estimated by tympanic measurements were smaller than those estimated by axillary measurements. This variation of axillary temperature may be due to changes in the measurement methods introduced by modern devices and techniques. However, axillary temperature values correlated well with those of tympanic measurements, suggesting that the technique may reliably report an individual's state of health. It is important for individuals to know their baseline axillary temperature to evaluate subsequent temperature measurements as normal or abnormal. Moreover, axillary temperature variations may, in part, reflect fat mass and changes due to the menstrual cycle.

Background: The aims of this study were to (1) evaluate whether recently introduced methods of measuring axillary temperature are reliable, (2) examine if individuals know their baseline body temperature based on an actual measurement, and (3) assess the factors affecting axillary temperature and reevaluate the meaning of the axillary temperature.
Methods: Subjects were healthy young men and women (n= 76 and n = 65, respectively). Three measurements were obtained: (1) axillary temperature using a digital thermometer in a predictive mode requiring 10 s (Tax-10 s), (2) axillary temperature using a digital thermometer in a standard mode requiring 10 min (Tax-10 min), and (3) tympanic membrane temperature continuously measured by infrared thermometry (T-ty). The subjects answered questions about eating and exercise habits, sleep and menstrual cycles, and thermoregulation and reported what they believed their regular body temperature to be (T-reg).
Results: T-reg, Tax-10 s, Tax-10 min, and T-ty were 36.2 +/- 0.4, 36.4 +/- 0.5, 36.5 +/- 0.4, and 36.8 +/- 0.3 degrees C (mean +/- SD), respectively. There were correlations between T-ty and Tax-10 min, T-ty and Tax-10 s, and Tax-10 min and Tax-10 s (r = .62, r = .46, and r = .59, respectively, P &lt; .001), but not between T-reg and Tax-10 s (r = .11, P = .20). A lower Tax-10 s was associated with smaller body mass indices and irregular menstrual cycles.
Conclusions: Modern devices for measuring axillary temperature may have changed the range of body temperature that is recognized as normal. Core body temperature variations estimated by tympanic measurements were smaller than those estimated by axillary measurements. This variation of axillary temperature may be due to changes in the measurement methods introduced by modern devices and techniques. However, axillary temperature values correlated well with those of tympanic measurements, suggesting that the technique may reliably report an individual's state of health. It is important for individuals to know their baseline axillary temperature to evaluate subsequent temperature measurements as normal or abnormal. Moreover, axillary temperature variations may, in part, reflect fat mass and changes due to the menstrual cycle.

Hyperosmolality in extracellular fluid in humans attenuates autonomic thermoregulation in heat, such as sweating and blood flow in the skin. However, exercise training minimizes the attenuation. The aim of the present study was to clarify the influence of hyperosmolality on thermal perception and to assess the training effect of exercise. Ten sedentary (SED) and 10 endurance-trained (TR) healthy young men were infused with 0.9% (normal saline [NS]) or 3% NaCl (hypertonic saline [HS]) for 120min on two separate days. After infusion for 20min, heat stimulus to the skin of the whole body was produced by a gradual increase in hot water-perfused suit temperature (33°C, 36°C, and 39°C), which was first used in the normothermic condition and then in the mild hyperthermic condition (0.5-0.6°C increase in esophageal temperature) and controlled by immersion of the lower legs in a water bath at 34.5°C and 42°C, respectively. Thermal sensation and comfort were rated at the time of each thermal condition. Plasma osmolality increased by ~10mosmL/kg·H2O in the HS trial. In the mild hyperthermic condition, increases in sweat rate and cutaneous vascular conductance were lower in the HS than in the NS trial in both the SED and TR groups (p<0.05). In the SED group, thermal sensation in the mild hyperthermic condition was lower in the HS than in the NS trial (p<0.05); there was no significant difference between the trials in the TR group. These results might indicate that hyperosmolality attenuates thermal sensation with heat and that exercise training eliminates the attenuation.

Thermoregulation is categorized as either autonomic (i.e., sweating, shivering) or behavioral (i.e., wearing clothes, usage of air conditioner) thermoregulation. Compared to autonomic thermoregulation, the neural pathway of behavioral thermoregulation in cold environments remains unclear. A decrease in ambient temperature is perceived through thermoreceptors for detecting cold, including transient receptor potential (TRP) channels, such as TRPM8 and TRPA1, which are expressed in the sensory nerve endings of the skin. From these receptors, nerves connect to the dorsal root ganglion and dorsal horn in the spinal cord, and arrive at the lateral parabrachial nucleus in the pons, which is the same neural pathway that is used for autonomic thermoregulation. Following this, an unknown neural pathway induces thermoregulatory behavior, such as cold-escape behavior. Both young and climacteric women complain of an unpleasant thermal comfort, which is attributed to &quot;hie-sho&quot; (chill or poor blood circulation). The altered thermal sensation and comfort by an absence or a fluctuation of estrogen (E2) may modulate behavioral thermoregulation in females. This effect is unknown in women. However, in

We assessed the relationship between core temperature (Tc) and sleep rhythms in mice, and examined the effects of ambient temperature and fasting. Tc, electroencephalograms (EEG), electromyograms (EMG), and spontaneous activity in male ICR mice (n=9) were measured by telemetry for 3 days under a 12:12h dark-light cycle. Mice were fed or fasted at an ambient temperature (Ta) of 27°C or 20°C for the final 30h of the experiment. The vigilance state was categorized into a wake state, rapid-eye movement (REM) sleep, and non-REM (NREM) sleep, and the total sleep time (TST) was assessed. Relationships between Tc and TST, NREM periods, and REM sleep were estimated using Pearson's correlation coefficient. During cold exposure, Tc decreased during the dark and light phases, and TST and the periods of NREM and REM sleep decreased during the dark phase. Throughout the fasting period, Tc also decreased during the dark and light phases. Furthermore, the decrease in Tc was augmented when fasting and cold were combined. TST and NREM sleep periods decreased in the light and dark phases, respectively, whereas REM sleep periods decreased in both phases. Negative linear correlations (r=-0.884 to -0.987) were observed between Tc and TST, NREM sleep periods, and REM sleep periods, except for Tc and REM sleep periods where fasting and cold conditions were combined. The correlations between sleep and Tc rhythms were well maintained during cold exposure and fasting. However, when cold and fasting were combined, REM sleep and Tc rhythms were desynchronized.

We investigated the effects of menstrual cycle phase on thermal sensation, thermal pleasantness, and autonomic thermoregulatory responses during mild cold exposure. Eight healthy young women participated. Experiments were conducted in the follicular and luteal phases: 120 min exposure at 23.5 °C after 40-min at a baseline temperature of 29 °C. Body core temperature was higher (P = 0.01) in the luteal phase than in the follicular phase. Thermal sensation of the whole body (P = 0.59), hands (P = 0.46), and toes (P = 0.94), and thermal pleasantness of the whole body (P = 0.79) were no different between phases. In both phases, mean skin temperature decreased (P = 0.00) in the same manner without any change in metabolic rate (P = 0.90). These results suggest the change of body core temperature in the menstrual cycle phases has no effect on thermal perception of cold or on autonomic cold-defense response.

It has been speculated that the control of core temperature is modulated by physiological demands. We could not prove the modulation because we did not have a good method to evaluate the control. In the present study, the control of core temperature in mice was assessed by exposing them to various ambient temperatures (Ta), and the influence of circadian rhythm and feeding condition was evaluated. Male ICR mice (n=20) were placed in a box where Ta was increased or decreased from 27°C to 40°C or to -4°C (0.15°C/min) at 0800 and 2000 (daytime and nighttime, respectively). Intra-abdominal temperature (Tcore) was monitored by telemetry. The relationship between Tcore and Ta was assessed. The range of Ta where Tcore was relatively stable (range of normothermia, RNT) and Tcore corresponding to the RNT median (regulated Tcore) were estimated by model analysis. In fed mice, the regression slope within the RNT was smaller in the nighttime than in the daytime (0.02 and 0.06, respectively), and the regulated Tcore was higher in the nighttime than in the daytime (37.5°C and 36.0°C, respectively). In the fasted mice, the slope remained unchanged, and the regulated Tcore decreased in the nighttime (0.05 and 35.9°C, respectively), while the slopes in the daytime became greater (0.13). Without the estimating individual thermoregulatory response such as metabolic heat production and skin vasodilation, the analysis of the Ta-Tcore relationship could describe the character of the core temperature control. The present results show that the character of the system changes depending on time of day and feeding conditions.

Cold defense mechanisms in mice are attenuated in the light phase during fasting, resulting in hypothermia. The present study examined whether specific neurons and areas in the SCN are related to the response. Mice were fasted over 47h or remained fed, during which they were placed at 20 or 27°C for 3h in the light or dark phases. Body temperature (Tb) was monitored. After the exposure, immunoreactive (IR) cells of cFos, arginine vasopressin (AVP), and vasoactive intestinal polypeptide (VIP) in the SCN were assessed. Tb at 20°C during fasting was lower in the light phase than in the dark phase. Both AVP/cFos-IR and VIP/cFos-IR cells increased when mice were at 20°C during fasting in the light phase. Such increase was observed in the central part of the SCN. These responses in the SCN may be related to the hypothermia in the light phase.

In a previous study, we investigated the contribution of the surface of the face, chest, abdomen, and thigh to thermal comfort by applying local temperature stimulation during whole-body exposure to mild heat or cold. In hot conditions, humans prefer a cool face, and in cold they prefer a warm abdomen. In this study, we extended investigation of regional differences in thermal comfort to the neck, hand, soles, abdomen (Experiment 1), the upper and lower back, upper arm, and abdomen (Experiment 2). The methodology was similar to that used in the previous study. To compare the results of each experiment, we utilized the abdomen as the reference area in these experiments. Thermal comfort feelings were not particularly strong for the limbs and extremities, in spite of the fact that changes in skin temperature induced by local temperature stimulation of the limbs and extremities were always larger than changes that were induced in the more proximal body parts. For the trunk areas, a significant difference in thermal comfort was not observed among the abdomen, and upper and lower back. An exception involved local cooling during whole-body mild cold exposure, wherein the most dominant preference was for a warmer temperature of the abdomen. As for the neck and abdomen, clear differences were observed during local cooling, while no significant difference was observed during local warming. We combined the results for the current and the previous study, and characterized regional differences in thermal comfort and thermal preference for the whole-body surface.

Fasted mice show torpor-like hypothermia in the cold in their inactive phase. The aim of the present study was to elucidate whether leptin and/or ghrelin are involved in this reaction and to identify its neurophysiological mechanisms. In ob/ob mice, which lack leptin, metabolic heat production (oxygen consumption, Vo(2)) was suppressed in 20°C cold in both the light and dark phases, resulting in hypothermia. When wild-type mice received a systemic injection of 8 µg ghrelin in the early light phase, followed by a 2-h cold exposure to 10°C, their core body temperature (T(b)) decreased by 1.7°C, and they displayed a less marked increase in Vo(2) compared with vehicle-injected mice. However, ghrelin injection in the early dark phase resulted in the maintenance of T(b) and increased Vo(2) in the mice, which was similar to the result observed in the vehicle-injected mice. The number of doubly labeled neurons with cFos and neuropeptide Y (NPY) in the suprachiasmatic nucleus was greater in the light phase in the ghrelin-injected mice, which may suggest that ghrelin activates NPY neurons. On the contrary, in the paraventricular nucleus, the counts became greater only when they were exposed to the cold in the dark phase. These results indicate that ghrelin plays an important role in inducing time-dependent changes in thermoregulation in the cold via hypothalamic pathways.

Rats place their tails underneath their body trunks when cold (tail-hiding behavior). The aim of the present study was to determine whether this behavior is necessary to maintain body temperature. Male Wistar rats were divided into 'fed' and '42-h fasting' groups. A one-piece tail holder (8.4 cm in length) that prevented the tail-hiding behavior or a three-piece tail holder (2.8 cm in length) that allowed for the tail-hiding behavior was attached to the tails of the rats. The rats were exposed to 27°C for 180 min or to 20°C for 90 min followed by 15°C for 90 min with continuous body temperature and oxygen consumption measurements. Body temperature decreased by -1.0 ± 0.1°C at 15°C only in the rats that prevented tail-hiding behavior of the 42-h fasting group, and oxygen consumption increased at 15°C in all animals. Oxygen consumption was not different between the rats that prevented tail-hiding behavior and the rats that allowed the behavior in the fed and 42-h fasting groups under ambient conditions. These results show that the tail-hiding behavior is involved in thermoregulation in the cold in fasting rats.

We evaluated the effect of plasma hyperosmolality on behavioral thermoregulation in mice, using a new experimental system. The system consisted of Plexiglas box (dimensions: 50×12×19 cm) with five computer-controlled Peltier boards (dimensions: 10×10 cm) at the bottom. Experiments were conducted in two different settings of the system. An operant behavior setting: each board was first set to 39°C, and the right-end board was changed to 20°C for 1 min when a mouse moved to a specific position. A temperature mosaic setting: each board was randomly set to 15°C, 22°C, 28°C, 35°C, or 39°C with a 6-min interval, but each board temperature was different from the others at a given time point. Mice were injected subcutaneous (s.c.) isotonic or hypertonic saline (154 mM (IS group) or 2,500 mM (HS group), 10 ml/kg body wt), and exposed to either setting for 90 min. In the operant setting, the HS group showed fewer operant behavior counts than the IS group (11±5 and 25±4 counts, respectively; P<0.05) with greater increase in body temperature (1.6±0.4°C vs. 0.0±0.2°C, respectively; P<0.05). In the mosaic setting, the HS group selected the board temperature of 35°C more frequently than the other temperatures (P<0.05) with the same increase in body temperature. These results may suggest that plasma hyperosmolality modulates behavioral thermoregulatory response to heat and induce regulated hyperthermia.

The sympathetic thermoregulatory system controls the magnitude of adaptive thermogenesis in correspondence with the environmental temperature or the state of energy intake and plays a key role in determining the resultant energy storage. However, the nature of the trigger initiating this reflex arc remains to be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we examined the involvement of specific activation of transient receptor potential (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic system by measuring the efferent activity of the postganglionic sympathetic nerve innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric administration of capsiate resulted in a time- and dose-dependent increase in integrated BAT sympathetic nerve activity (SNA) over 180 min, which was characterized by an emergence of sporadic high-activity phases composed of low-frequency bursts. This increase in BAT SNA was abolished by blockade of TRP channels as well as of sympathetic ganglionic transmission and was inhibited by ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited to BAT and did not occur in the heart or pancreas. These results point to a neural pathway enabling the selective activation of the central network regulating the BAT SNA in response to a specific stimulation of gastrointestinal TRP channels and offer important implications for understanding the dietary-dependent regulation of energy metabolism and control of obesity.

The present study examined the effect of the central administration of estrogen on responses to the cold. Estrogen or cholesterol was applied locally to the medial preoptic nucleus (MPO) or dorsomedial hypothalamic nucleus (DMH) of the hypothalamus in free-moving ovariectomized rats. Forty-eight hours after the application, rats had 2-h exposure at 10 or 25 degrees C. Body temperature (T(b)) and the tail surface temperature (T(tail)) were continuously measured by telemetry and thermography, respectively. The change of T(b) at 10 degrees C from the 25 degrees C baseline was higher in the estrogen application in the MPO than that in the cholesterol application; however, such difference was not observed in the DMH application. The uncoupling 1 protein mRNA level in the interscapular brown adipose tissue involved in non-shivering thermogenesis was not different between the estrogen and cholesterol applications in the MPO and DMH. T(tail) decreased in the cold, which was greater after the estrogen application in the MPO than after the cholesterol application. These results show that estrogen affects the MPO in female rats, changing T(b) in the cold. Moreover, suppression of heat loss from the tail may be involved in the mechanism.

:The present study examined the effect of the central administration of estrogen on responses to the cold. Estrogen or cholesterol was applied locally to the medial preoptic nucleus (MPO) or dorsomedial hypothalamic nucleus (DMH) of the hypothalamus in free-moving ovariectomized rats. Forty-eight hours after the application, rats had 2-h exposure at 10 or 25 degrees C. Body temperature (T(b)) and the tail surface temperature (T(tail)) were continuously measured by telemetry and thermography, respectively. The change of T(b) at 10 degrees C from the 25 degrees C baseline was higher in the estrogen application in the MPO than that in the cholesterol application; however, such difference was not observed in the DMH application. The uncoupling 1 protein mRNA level in the interscapular brown adipose tissue involved in non-shivering thermogenesis was not different between the estrogen and cholesterol applications in the MPO and DMH. T(tail) decreased in the cold, which was greater after the estrogen application in the MPO than after the cholesterol application. These results show that estrogen affects the MPO in female rats, changing T(b) in the cold. Moreover, suppression of heat loss f

Hypohydration caused by exercise in the heat attenuates autonomic thermoregulation such as sweating and skin blood flow in humans. In contrast, it remains unknown if behavioral thermoregulation is modulated during hypohydration. We assume that thermal unpleasantness could drive the behavioral response, and would also be modulated during hypohydration. Nine healthy young men participated in the present study. Body and skin temperatures were monitored. Ratings of thermal sensation and pleasantness were conducted. After approximately 45 min rest at 27 degrees C, they performed 50-min cycling exercise, which was at the level of 40% of heart rate range at 35 degrees C (hypohydration trial) or at the level of 10% of heart rate range at 23 degrees C (control trial), respectively. Subjects returned to the rest at 27 degrees C, and the ambient temperature was then changed from 22 to 38 degrees C. Body weight decreased by 0.9+/-0.1% immediately after exercise in the hypohydration trial and 0.3+/-0.1% in the control trial. In the cold, no significant difference in thermal sensation or pleasantness was observed between trials. There was no significant difference in thermal pleasantness between trials in the heat, although thermal sensation in the heat (32.5-36 degrees C) was significantly lower in the hypohydration trial than in the control trial. In addition, laser Doppler flow of the skin and sweat rate were attenuated in the heat in the hypohydration trial. These results may indicate that mild hypohydration after exercise in the heat has no influence on behavioral responses to the heat.

We would like to emphasize about the system involved with homeostatic maintenance of body temperature. First, the primary mission of the thermoregulatory system is to defend core temperature (T (core)) against changes in ambient temperature (T (a)), the most frequently encountered disturbance for the system. T (a) should be treated as a feedforward input to the system, which has not been adequately recognized by thermal physiologists. Second, homeostatic demands from outside the thermoregulatory system may require or produce an altered T (core), such as fever (demand from the immune system). There are also conditions where some thermoregulatory effectors might be better not recruited due to demands from other homeostatic systems, such as during dehydration or fasting. Third, many experiments have supported the original assertion of Satinoff that multiple thermoregulatory effectors are controlled by different and relatively independent neuronal circuits. However, it would also be of value to be able to characterize strictly regulatory properties of the entire system by providing a clear definition for the level of regulation. Based on the assumption that T (core) is the regulated variable of the thermoregulatory system, regulated T (core) is defined as the T (core) that pertains within the range of normothermic T (a) (Gordon in temperature and toxicology: an integrative, comparative, and environmental approach, CRC Press, Boca Raton, 2005), i.e., the T (a) range in which an animal maintains a stable T (core). The proposed approach would facilitate the categorization and evaluation of how normal biological alterations, physiological stressors, and pathological conditions modify temperature regulation. In any case, of overriding importance is to recognize the means by which an alteration in T (core) (and modification of associated effector activities) increases the overall viability of the organism.

The aim of this study was to determine whether estrogen modulates central and peripheral responses to cold in female rats. In ovariectomized female rats with and without administered estrogen [E(2) (+) and E(2) (-), respectively], the counts of cFos-immunoreactive cells in the medial preoptic nucleus (MPO) and dorsomedial hypothalamic nucleus (DMH) in the hypothalamus were greater in the E(2) (+) rats than in the E(2) (-) rats at 5 degrees C. Examination of the response of normal female rats to exposure to 5 degrees C at different phases of the estrus cycle revealed that counts of cFos-immunoreactive cells in the MPO, DMH, and posterior hypothalamus and the level of uncoupling protein 1 mRNA in the brown adipose tissues were greater in the proestrus phase than on day 1 of the diestrus phase. This result was linked to the level of plasma estrogen. The body temperature during cold exposure was higher in the E(2) (+) rats than in the E(2) (-) rats and was also higher in the proestrus phase than on day 1 of the diestrus phase. We conclude that estrogen may affect central and peripheral responses involved in thermoregulation in the cold.

The circadian rhythm of body temperature (Tb) is a well-known phenomenon. However, it is unknown how the circadian system including the suprachiasmatic nucleus (SCN) and clock genes affects thermoregulation. Food deprivation in mice induces a greater reduction of Tb particularly in the light phase. We examined the role of Clock, one of key clock genes and the SCN during induced hypothermia. At 20 °C with fasting, mice increased their metabolic heat production in the dark phase and maintained Tb, whereas in the light phase, heat production was less, resulting in hypothermia. Under these conditions, neuronal activity in the SCN, assessed by cFos expression, increased only in the light phase. However, such differences in thermoregulatory and neural responses between the phases in Clock mutant mice were less marked. The neural network between the SCN and paraventricular nucleus appeared to be important in hypothermia. These findings suggest that the circadian system per se is influenced by both the feeding condition and environmental temperature and that it modulates thermoregulation. © 2009 IBRO.

Sensations evoked by thermal stimulation (temperature-related sensations) can be divided into two categories, "temperature sensation" and "thermal comfort." Although several studies have investigated regional differences in temperature sensation, less is known about the sensitivity differences in thermal comfort for the various body regions. In the present study, we examined regional differences in temperature-related sensations with special attention to thermal comfort. Healthy male subjects sitting in an environment of mild heat or cold were locally cooled or warmed with water-perfused stimulators. Areas stimulated were the face, chest, abdomen, and thigh. Temperature sensation and thermal comfort of the stimulated areas were reported by the subjects, as was whole body thermal comfort. During mild heat exposure, facial cooling was most comfortable and facial warming was most uncomfortable. On the other hand, during mild cold exposure, neither warming nor cooling of the face had a major effect. The chest and abdomen had characteristics opposite to those of the face. Local warming of the chest and abdomen did produce a strong comfort sensation during whole body cold exposure. The thermal comfort seen in this study suggests that if given the chance, humans would preferentially cool the head in the heat, and they would maintain the warmth of the trunk areas in the cold. The qualitative differences seen in thermal comfort for the various areas cannot be explained solely by the density or properties of the peripheral thermal receptors and thus must reflect processing mechanisms in the central nervous system.

We investigated the effects of alcohol on thermoregulatory responses and thermal sensations during cold exposure in humans. Eight healthy men (mean age 22.3+/-0.7 year) participated in this study. Experiments were conducted twice for each subject at a room temperature of 18 degrees C. After a 30-min resting period, the subject drank either 15% alcohol at a dose of 0.36 g/kg body weight (alcohol session) or an equal volume of distilled water (control session), and remained in a sitting position for another 60 min. Mean skin temperature continued to decrease and was similar in control and alcohol sessions. Metabolic rate was lower in the alcohol session, but the difference did not affect core temperature, which decreased in a similar manner in both alcohol and control sessions (from 36.9+/-0.1 degrees C to 36.6+/-0.1 degrees C). Whole body sensations of cold and thermal discomfort became successively stronger in the control session, whereas these sensations were both greatly diminished after drinking alcohol. In a previous study we performed in the heat, using a similar protocol, alcohol produced a definite, coordinated effect on all autonomic and sentient heat loss effectors. In the current study in the cold, as compared to responses in the heat, alcohol intake was followed by lesser alterations in autonomic effector responses, but increased changes in sensations of temperature and thermal discomfort. Overall, our results indicate that although alcohol influences thermoregulation in the cold as well as in the heat, detailed aspects of the influence are quite different.

Introduction Dehydration attenuates autonomic thermoregulation in the heat such as sweating and skin blood flow in human. Hyperosmolality in the extracellular fluid is thought to be involved in this mechanism. In contrast, behavioral thermoregulation (i.e. heat escape behavior) is augmented after hypertonic saline injection in rats (Nagashima et al., Am J Physiol 2001). However, it remains unknown if human activate behavioral thermoregulation during dehydration. Methods Ten healthy young men participated in the present study. Body and skin temperature were monitored. Rating for thermal sensation and comfort were conducted. After 45 min rest at 27&deg;C, they did 50 min ergometer exercise, which was at the level of 40% peak VO₂ or 15% peak VO₂ at an ambient temperature of 35&deg;C or 24&deg;C, respectively. Subjects returned to the rest at 27&deg;C until body and skin temperature being restored. Ambient temperature was then changed from 22&deg;C to 38&deg;C. Results Body weight decreased by 1.1 &plusmn; 0.1% after the exercise at 35&deg;C and 0.2 &plusmn; 0.1% at 24&deg;C. Plasma osmolality increased by 6 &plusmn; 1 mosmol/kg H₂O at 35&deg;C, but did not change at &sim;24&deg;C. Thermal sensation and comfort in the heat were augmented (i.e. feeling hotter and more uncomfortable) after the exercise at 35&deg;C. Conclusion Dehydration increases thermal sensation and comfort in the heat in human, which are closely related to behavioral thermoregulation. [J Physiol Sci. 2008;58 Suppl:S103]

We tested the hypothesis that peripheral vascular responses (in the lower and upper limbs) to application of lower body positive pressure (LBPP) are dependent on the posture of the subjects. We measured heart rate, stroke volume, mean arterial pressure, leg and forearm blood flow (using the Doppler ultrasound technique), and leg (LVC) and forearm (FVC) vascular conductance in 11 subjects (9 men, 2 women) without and with LBPP (25 and 50 mmHg) in supine and upright postures. Mean arterial pressure increased in proportion to increases in LBPP and was greater in supine than in upright subjects. Heart rate was unchanged when LBPP was applied to supine subjects but was reduced in upright ones. Leg blood flow and LVC were both reduced by LBPP in supine subjects [LVC: 4.8 (SD 4.0), 3.6 (SD 3.5), and 1.4 (SD 1.8) ml.min(-1).mmHg(-1) before LBPP and during 25 and 50 mmHg LBPP, respectively; P < 0.05] but were increased in upright ones [LVC: 2.0 (SD 1.2), 3.4 (SD 3.4), and 3.0 (SD 2.0) ml.min(-1).mmHg(-1), respectively; P < 0.05]. Forearm blood flow and FVC both declined when LBPP was applied to supine subjects [FVC: 1.3 (SD 0.6), 1.0 (SD 0.4), and 0.9 (SD 0.6) ml. min(-1).mmHg(-1), respectively; P < 0.05] but remained unchanged in upright ones [FVC: 0.7 (SD 0.4), 0.7 (SD 0.4), and 0.6 (SD 0.5) ml.min(-1).mmHg(-1), respectively]. Together, these findings indicate that the leg vascular response to application of LBPP is posture dependent and that the response differs in the lower and upper limbs when subjects assume an upright posture.

INTRODUCTION It is well known that body temperature in female is closely linked with menstrual cycle. We reported that estrogen affects thermal regulation in rats: 1) estrogen is involved in circadian body temperature rhythm; 2) estrogen has an important role in thermal regulation in both the heat and cold. Moreover, in human beings, not a small population of females experiences some troubles in thermoregulation such as hot flash or cold sensation. Estrogen replacement therapy is sometimes effective for the females. In this study, we hypothesized that there would be differences in thermoregulation and thermal sensation, depending of menstruation cycle. METHOSDS and RESULTS Eight female subjects with a regular menstruation participated in this study. Experiments were conducted twice for each subject in follicular (F) and luteal (L) phases, determined by basal body temperature. Experimental condition was 120-min exposure at 23.5&deg;C after a 40-min baseline at 29.5&deg;C. Mean skin temperature decreased and body core temperature increased in both F and L during the 23.5&deg;C exposure. Oxygen consumption also increased in F and L. Based on rating scores for thermal sensation and comfort, L enhanced both coldness and unpleasantness when ambient temperature changed from 29.5&deg;C to 23.5&deg;C. COMCLUSION Although the autonomic thermal regulation seems to be similar between F and L, the menstrual phase may have an influence on thermal sensation or comfort. Estrogen may be involved in this mechanism. [J Physiol Sci. 2007;57 Suppl:S183]

Systemic salt loading has been reported to facilitate operant heat-escape/cold-seeking behavior. In the present study, we hypothesized that the median preoptic nucleus (MnPO) would be involved in this mechanism. Rats were divided into two groups (n = 6 each): one group had the MnPO lesion with ibotenic acid (4.0 mug) and the other was the vehicle control. After subcutaneous injection (10 ml/kg) of either isotonic- (154 mM) or hypertonic-saline (2,500 mM), each rat was placed in a behavior box, where the ambient temperature was changed to 26 degrees C, 35 degrees C, and 40 degrees C every 1 h. The position of a rat in the box and the body core temperature (T(core)) were monitored. A rat could trigger 0 degrees C air for 45 s in the 35 degrees C and 40 degrees C heat when moved in a specific area in the box (operant behavior). In the control group, counts of the operant behavior were greater (P < 0.05) in the hypertonic- than in the isotonic-saline injection (17 +/- 2 and 10 +/- 2 at 35 degrees C, 24 +/- 2 and 18 +/- 1 at 40 degrees C). T(core) remained unchanged throughout the exposure, although the level was lower (P < 0.05) in the hypertonic- than in the isotonic-saline trial (36.6 +/- 0.2 degrees C and 37.4 +/- 0.1 degrees C at 26 degrees C and 36.9 +/- 0.2 degrees C and 37.4 +/- 0.1 degrees C at 40 degrees C, respectively). However, in the MnPO-lesion group, counts of the behavior were similar between the hypertonic- and isotonic-saline injection trials (10 +/- 2 and 8 +/- 1 at 35 degrees C, and 17 +/- 1 and 16 +/- 1 at 40 degrees C, respectively). T(core) increased (P < 0.05) in the heat in both trials (36.8 +/- 0.1 degrees C and 37.4 +/- 0.1 degrees C at 26 degrees C and 37.4 +/- 0.2 degrees C and 37.8 +/- 0.2 degrees C at 40 degrees C in the hypertonic- and isotonic-saline injection trials, respectively). These results may suggest that, at least in part, the MnPO is involved in the facilitation of heat-escape/cold-seeking behavior during osmotic stimulation.

We report a new system for monitoring sensations of many body parts as well as comprehensively showing the distribution of overall skin temperature (T(sk)) and temperature-related sensations. The system consists of a console with 52 levers to report temperature-related sensations and software that facilitates the visualization of the distribution of T(sk) and temperature-related sensations by displaying them on a model of the human body. The system's utility was demonstrated with a physiological experiment involving three males and three females. They were exposed to step changes of ambient temperature from 23 degrees C to 33 degrees C. We measured T(sk) at 50 points, and the subjects concurrently provided estimates of local temperature sensation and thermal comfort/discomfort at 25 loci. This system greatly facilitates the perception and analysis of spatial relationships and differences in temperature and sensation in various areas of the body.

Homeothermic animals regulate body temperature by autonomic and behavioral thermoeffector responses. The regulation is conducted mainly in the brain. Especially, the preoptic area (PO) in the hypothalamus plays a key role. The PO has abundant warm-sensitive neurons, sending excitatory signals to the brain regions involved in heat loss mechanisms, and inhibitory signals to those involved in heat production mechanisms. The sympathetic fibers determine tail blood flow in rats, which is an effective heat loss process. Some areas in the midbrain and medulla are involved in the control of tail blood flow. Recent study also showed that the hypothalamus is involved in heat escape behavior in rats. However, our knowledge about behavioral regulation is limited. The central mechanism for thermal comfort and discomfort, which induce various behavioral responses, should be clarified. In the heat, dehydration affects both autonomic and behavioral thermoregulation by non-thermoregulatory factors such as high Na+ concentration. The PO seems to be closely involved in these responses. The knowledge about the central mechanisms involved in thermoregulation is important to improve industrial health, e.g. preventing accidents associated with the heat or organizing more comfortable working environment.

The nature of muscle efferent fibre activation during whole body cooling was investigated in urethane-anaesthetized rats. Multiunit efferent activity to the gastrocnemius muscle was detected when the trunk skin was cooled by a water-perfused jacket to below 36.0 +/- 0.7 degrees C. That efferent activity was not blocked by hexamethonium (50 mg kg(-1), i.v.) and was not associated with movement or electromyographic activity. Cold-induced efferent activity enhanced the discharge of afferent filaments from the isotonically stretched gastrocnemius muscle, demonstrating that it was fusimotor. Fusimotor neurons were activated by falls in trunk skin temperature, but that activity ceased when the skin was rewarmed, regardless of how low core temperature had fallen. While low core temperature alone was ineffective, a high core temperature could inhibit the fusimotor response to skin cooling. Fusimotor activation by skin cooling was often accompanied by desynchronization of the frontal electroencephalogram (EEG), but was not a simple consequence of cortical arousal, in that warming the scrotum desynchronized the EEG without activating fusimotor fibres. Inhibition of neurons in the rostral medullary raphé by microinjections of glycine (0.5 m, 120-180 nl) reduced the fusimotor response to skin cooling by 95 +/- 3%, but did not prevent the EEG response. These results are interpreted as showing a novel thermoregulatory reflex that is triggered by cold exposure. It may underlie the increased muscle tone that precedes overt shivering, and could also serve to amplify shivering. Like several other cold-defence responses, this reflex depends upon neurons in the rostral medullary raphé.

In this study, we developed a heat and steam generating (HSG) sheet that generates steam for several hours, and analyzed its effects on thermoregulatory responses and thermal sensation. In seven healthy male subjects the lumbar region (lower back) was warmed for four hours in a cool environment of 20&deg;C and 40%RH. For each subject, three experiments were performed: 1) warming the lower back with a HSG sheet (12&times;20 cm), 2) warming with a heat generating (HG) sheet without steam, and 3) no warming (control). The skin and subcutaneous temperatures in and around the warmed area, as well as rectal temperature were measured. The subjects reported whole body thermal comfort, and local sensations in the warmed area. While the temperature under the sheet was similar between the HSG and HG sheets (approximately 38.5&deg;C), skin temperature at 2 cm from the sheet was about 0.9&deg;C higher (p<0.05) for the HSG sheet than the HG sheet. The subjects reported less whole body coldness during the warming by the HSG sheet than the HG sheet. They also reported stronger and more spreading warm sensation in the warmed region for the HSG sheet than the HG sheet. In a separate experiment using an apparatus with a heat flux sensor, higher heat flux was observed for the HSG sheet than the HG sheet, even though both sheets gave the same surface temperature. These results suggest that warming the skin with steam is more efficient than warming it with dry air.<br>

We investigated the effects of alcohol on thermoregulatory responses and thermal sensations during mild heat exposure in humans. Eight healthy men participated in this study. Experiments were conducted twice for each subject at a room temperature of 33 degrees C. After a 30-min resting period, the subject drank either 15% alcohol (alcohol session) at a dose of 0.36 g/kg body weight or equal volume of water (control session). Skin blood flow and chest sweat rate in the alcohol session significantly increased over those in controls 10 min after drinking. Deep body temperature in the alcohol session started to decrease 20 min after the onset of sweating and eventually fell 0.3 degrees C lower than in the controls. Whole body hot sensation transiently increased after alcohol drinking, whereas it changed little after water drinking. The increased "hot" sensation would presumably cause cool-seeking behavior, if permitted. Thus, alcohol influences thermoregulation so that body core temperature is lowered not only by automatic mechanisms (sweating and skin vasodilation) but also behaviorally. These results suggest that decreases in body temperature after alcohol drinking are not secondary to skin vasodilation, a well-known effect of alcohol, but rather result from a decrease in the regulated body temperature evidenced by the coordinated modulation of various effectors of thermoregulation and sensation.

Sensations evoked by innocuous thermal stimulation can be divided into two categories. One is "temperature sensation" in a narrow sense, which is directed towards an object outside the body. The other is the "thermal comfort/discomfort" of the body that is important for thermoregulation. We recently reported rCBF changes in the amygdala which correlated with thermal comfort during whole body cooling (Kanosue et al., 2000). In the present study we investigated the region of brain that is activated by local thermal stimulation of the hand. Eight healthy subjects were recruited and gave written informed consent to participate in the study. Warm (39 degrees C) or cold (25 degrees C) stimuli was applied to the right or left hand for 30 s by using a water circulating tube that covered the whole hand. Each subject reported the magnitude of the stimulus intensity of temperature sensation using a scale from 1 (very cold) to 9 (very hot). All subjects reported hot or cold sensations and not pain. We examined the correlation between the rating scores and regional activity over the entire brain with a 3 Tesla MR imagers (VP, General Electrics, Milwaukee, US). Activation was observed in the contralateral secondary somatosensory cortex in response to both warm and cold stimulation of the hand. No activation was observed in the amygdala. This suggests that temperature sensation and thermal comfort might be generated by completely different structures of the brain.

Sensations evoked by innocuous thermal stimulation can be divided into two categories. One is "temperature sensation" in a narrow sense, which is directed towards an object outside the body. The other is the "thermal comfort/discomfort" of the body that is important for thermoregulation. We recently reported rCBF changes in the amygdala which correlated with thermal comfort during whole body cooling (Kanosue et al., 2000). In the present study we investigated the region of brain that is activated by local thermal stimulation of the hand. Eight healthy subjects were recruited and gave written informed consent to participate in the study. Warm (39 degrees C) or cold (25 degrees C) stimuli was applied to the right or left hand for 30 s by using a water circulating tube that covered the whole hand. Each subject reported the magnitude of the stimulus intensity of temperature sensation using a scale from 1 (very cold) to 9 (very hot). All subjects reported hot or cold sensations and not pain. We examined the correlation between the rating scores and regional activity over the entire brain with a 3 Tesla MR imagers (VP, General Electrics, Milwaukee, US). Activation was observed in the contralateral secondary somatosensory cortex in response to both warm and cold stimulation of the hand. No activation was observed in the amygdala. This suggests that temperature sensation and thermal comfort might be generated by completely different structures of the brain.

The criptochrome genes (Cry1 and Cry2) are involved in the molecular mechanism that controls the circadian clock, and mice lacking these genes (Cry1(-/-)/Cry2(-/-)) are behaviorally arrhythmic. It has been speculated that the circadian clock modulates the characteristics of thermoregulation, resulting in body temperature (T(b)) rhythm. However, there is no direct evidence proving this speculation. We show here that T(b) and heat production in Cry1(-/-)/Cry2(-/-) mice are arrhythmic under constant darkness. In contrast, both rhythms occur under a light-dark cycle and/or periodical food restriction linked with spontaneous activity and/or eating, although they are not robust as those in wild-type mice. The relationship between heat production and T(b) in Cry1(-/-)/Cry2(-/-) mice is linear and identical under any conditions, indicating that their T(b) rhythm is determined by heat production rhythm associated with activity and eating. However, T(b) in wild-type mice is maintained at a relatively higher level in the active phase than the inactive phase regardless of the heat production level. These results indicate that the thermoregulatory responses are modulated according to the circadian phase, and the Cry genes are involved in this mechanism.

The hypothalamus, especially the preoptic area, plays a crucial role in thermoregulation, and our previous studies showed that the periaqueductal gray matter is important for transmitting efferent signals to thermoregulatory effectors in rats. Neurons responsible for skin vasodilation are located in the lateral portion of the rostral periaqueductal gray matter, and neurons that mediate non-shivering thermogenesis are located in the ventrolateral part of the caudal periaqueductal gray matter. We investigated the distribution of neurons in the rat hypothalamus that are activated by exposure to neutral (26 degrees C), warm (33 degrees C), or cold (10 degrees C) ambient temperature and project to the rostral periaqueductal gray matter or caudal periaqueductal gray matter, by using the immunohistochemical analysis of Fos and a retrograde tracer, cholera toxin-b. When cholera toxin-b was injected into the rostral periaqueductal gray matter, many double-labeled cells were observed in the median preoptic nucleus in warm-exposed rats, but few were seen in cold-exposed rats. On the other hand, when cholera toxin-b was injected into the caudal periaqueductal gray matter, many double-labeled cells were seen in a cell group extending from the dorsomedial nucleus through the dorsal hypothalamic area in cold-exposed rats but few were seen in warm-exposed rats. These results suggest that the rostral periaqueductal gray matter receives input from the median preoptic nucleus neurons activated by warm exposure, and the caudal periaqueductal gray matter receives input from neurons in the dorsomedial nucleus/dorsal hypothalamic area region activated by cold exposure. These efferent pathways provide a substrate for thermoregulatory skin vasomotor response and non-shivering thermogenes is, respectively. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.

We surveyed the neural substrata for behavioral thermoregulation with immunohistochemical analysis of the expression of Fos protein in the rat brain. We used an operant system in which a rat exposed to heat (40 degrees C) could get cold air (0 degrees C) for 30 s when it moved into the reward area. Rats moved in and out of the reward area of the system periodically and thus maintained their body temperature at a normal level. In the rats performing heat escape behavior (active group), strong Fos immunoreactivity (Fos-IR) was found in the median preoptic nucleus (MnPO), parastrial nucleus (PS), and dorsomedial hypothalamus (DMH) compared with the controls. Another group of rats (passive group) were given the same temperature changes, regardless of the rat's movement, as those obtained by rats of the active group. Fos-IR in the MnPO was also seen in this group. The present results suggest that the PS and DMH play an important role in the genesis of thermoregulatory behavior, whereas the MnPO may be important for detecting changes in ambient and/or body temperatures.

The reduction of body core temperature (Tcore) after salt loading has been reported. In this study, we tested the hypothesis that, during a cold exposure in rats, (1) salt loading would decrease metabolic rate (MR), reducing Tcore, but (2) Tcore would be maintained when cold-escape/warm-seeking behaviour is available. In the first experiment (n = 7), MR and Tcore were measured by indirect calorimetry and telemetry, respectively, during 26, 20 and 10 degrees C exposure for 1 h each, in that order. In the second experiment (n = 7), each rat was placed in an operant system during the same exposure protocol as in the first experiment, where it could trigger a 40 degrees C air reward for 30 s at 20 and 10 degrees C by moving into specific areas (operant behaviour). In each experiment, rats repeated the same protocol twice with a subcutaneous injection (10 ml kg-1) of either isotonic saline (154 mM) or hypertonic saline (2500 mM). In the first experiment, MR in the isotonic-saline trial increased (P < 0.05) at 20 and 10 degrees C compared with that at 26 degrees C by 21 +/- 5 and 48 +/- 6 %, respectively (means +/- S.E.M.), with Tcore unchanged. However, values for MR and Tcore in the hypertonic-saline trial were lower (P < 0.05) than those in the isotonic-saline trial in any ambient temperature. In the second experiment, Tcore was also lower (P < 0.05) in the hypertonic-saline trial than in the isotonic-saline trial. The counts of the operant behaviour in the hypertonic-saline trial remained unchanged in each exposure period, but those in the isotonic-saline trial increased (P < 0.05) at 10 degrees C. These results may suggest that salt loading attenuates both metabolic and behavioural thermoregulatory responses to the cold.

To investigate the mechanism involved in the reduction of body core temperature (T(core)) during fasting in rats, which is selective in the light phase, we measured T(core), surface temperature, and oxygen consumption rate in fed control animals and in fasted animals on day 3 of fasting and day 4 of recovery at an ambient temperature (T(a)) of 23 degrees C by biotelemetry, infrared thermography, and indirect calorimetry, respectively. On the fasting day, 1) T(core) in the light phase decreased (P < 0.05) from the control; however, T(core) in the dark phase was unchanged, 2) tail temperature fell from the control (P < 0.05, from 30.7 +/- 0.1 to 23.9 +/- 0.1 degrees C in the dark phase and from 29.4 +/- 0.1 to 25.2 +/- 0.2 degrees C in the light phase), 3) oxygen consumption rate decreased from the control (P < 0.05, from 24.37 +/- 1.06 to 16.24 +/- 0.69 ml. min(-1). kg body wt(-0.75) in the dark phase and from 18.91 +/- 0.64 to 14.00 +/- 0.41 ml. min(-1). kg body wt(-0.75) in the light phase). All these values returned to the control levels on the recovery day. The results suggest that, in the fasting condition, T(core) in the dark phase was maintained by suppression of the heat loss mechanism, despite the reduction of metabolic heat production. In contrast, the response was weakened in the light phase, decreasing T(core) greatly. Moreover, the change in the regulation of tail blood flow was a likely mechanism to suppress heat loss.

To investigate the mechanism involved in the reduction of body core temperature (T-core) during fasting in rats, which is selective in the light phase, we measured T-core, surface temperature, and oxygen consumption rate in fed control animals and in fasted animals on day 3 of fasting and day 4 of recovery at an ambient temperature (T-a) of 23 degreesC by biotelemetry, infrared thermography, and indirect calorimetry, respectively. On the fasting day, 1) T-core in the light phase decreased (P &lt; 0.05) from the control; however, T-core in the dark phase was unchanged, 2) tail temperature fell from the control (P &lt; 0.05, from 30.7 +/- 0.1 to 23.9 +/- 0.1 degreesC in the dark phase and from 29.4 +/- 0.1 to 25.2 +/- 0.2 degreesC in the light phase), 3) oxygen consumption rate decreased from the control ( P &lt; 0.05, from 24.37 +/- 1.06 to 16.24 +/- 0.69 ml . min(-1) . kg body wt(-0.75) in the dark phase and from 18.91 +/- 0.64 to 14.00 +/- 0.41 ml . min(-1) . kg body wt(-0.75) in the light phase). All these values returned to the control levels on the recovery day. The results suggest that, in the fasting condition, T-core in the dark phase was maintained by suppression of the heat loss mechanism, despite the reduction of metabolic heat production. In contrast, the response was weakened in the light phase, decreasing T-core greatly. Moreover, the change in the regulation of tail blood flow was a likely mechanism to suppress heat loss.

Thermogenesis in the brown adipose tissue (BAT) is activated by the stimulation of the ventromedial hypothalamic nucleus (VMH). Local warming of the preoptic area (PO) suppresses this response. Injection of the GABA(A) receptor antagonist bicuculline into the caudal periaqueductal gray (cPAG), where excitatory neurons for BAT thermogenesis are located, did not influence the suppressive effect of PO warming. On the other hand, after bicuculline injection into the raphé pallidus, where excitatory neurons for BAT thermogenesis are also located, VMH stimulation produced BAT thermogenesis even during PO warming. The present results suggest that the inhibitory signal from the PO reaches the raphé pallidus and not the cPAG for the control of BAT thermogenesis.

Thermogenesis in the brown adipose tissue (BAT) is activated by the stimulation of the ventromedial hypothalamic nucleus (VMH). Local warming of the preoptic area (PO) suppresses this response. Injection of the GABA, receptor antagonist bicuculline into the caudal periaqueductal gray (cPAG), where excitatory neurons for BAT thermogenesis are located, did not influence the suppressive effect of PO warming. On the other hand, after bicuculline injection into the raphe pallidus, where excitatory neurons for BAT thermogenesis are also located, VMH stimulation produced BAT thermogenesis even during PO warming. The present results suggest that the inhibitory signal from the PO reaches the raphe pallidus and not the cPAG for the control of BAT thermogenesis. (C) 2002 Elsevier Science B.V. All rights reserved.

Salt loading decreases body core temperature (T(core)) at neutral ambient temperature (26 degrees C) and increases heat-escape/cold-seeking behaviour in desalivated rats. In this study, we tested the hypothesis that brain angiotensin II (AII) and arginine vasopressin (AVP) are associated with these responses. Surgically desalivated rats (n = 28) were administered an injection (S.C., 10 ml kg(-1)) of either normal saline (154 mM, NS) or hypertonic saline (2500 mM, HS) following an intracerebroventricular injection (10 microl kg(-1)) of an AII AT(1)-receptor antagonist (candesartan, 5 microg microl(-1)), an AVP V(1)-receptor antagonist ((beta-mercapto-beta, beta-cyclopenta-methylene propionyl(1), O-Me-Tyr(2), Arg(8))-vasopressin, 0.5 microg microl(-1)), or normal saline (154 mM). Each rat was placed in a behaviour box, first at 26 degrees C for 1 h to allow the measurement of baseline T(core) and movement. The ambient temperature was then elevated to 40 degrees C for the next 2 h, during which time the rat was able to trigger a 0 degrees C air reward for 30 s by moving into a specific area of the box (operant behaviour). The S.C. HS significantly decreased baseline T(core) at 26 degrees C (36.5 +/- 0.1 degrees C) and increased counts of operant behaviour at 40 degrees C (57 +/- 3) compared with results obtained following S.C. NS injection (37.4 +/- 0.1 degrees C and 42 +/- 1, respectively). These responses to s.c. HS were inhibited by the intracerebroventricular injection of AT(1) (37.3 +/- 0.1 degrees C and 43 +/- 2, respectively; P < 0.05) and V(1) antagonists (37.2 +/- 0.2 degrees C and 42 +/- 2, respectively; P < 0.05), although administration of both antagonists with S.C. NS had no effect. These results suggest that brain AII and AVP are involved in the decrease in T(core) observed at neutral ambient temperature and the increase in heat-escape/cold-seeking behaviour in response to osmotic stimulation, via the central AT(1) and V(1) receptors, respectively

Salt loading decreases body core temperature (T-core) at neutral ambient temperature (26degreesC) and increases heat-escape/cold-seeking behaviour in desalivated rats. In this study, we tested the hypothesis that brain angiotensin II (AII) and arginine vasopressin (AVP) are associated with these responses. Surgically desalivated rats (n = 28) were administered an injection (s.c., 10 ml kg(-1)) of either normal saline (154 mm, NS) or hypertonic saline (2500 mm, HS) following an intracerebroventricular injection (10 mul kg(-1)) of an AII AT(1)-receptor antagonist (candesartan, 5 mug mul(-1)), an AVP V-1-receptor antagonist ((beta-mercapto-beta, beta-cyclopenta-methylene propionyl(1), O-Me-Tyr(2), Arg(8))- vasopressin, 0.5 mug mul(-1)), or normal saline (154 mm). Each rat was placed in a behaviour box, first at 26degreesC for 1 h to allow the measurement of baseline T-core and movement. The ambient temperature was then elevated to 40 degreesC for the next 2 h, during which time the rat was able to trigger a 0 degreesC air reward for 30 s by moving into a specific area of the box (operant behaviour). The s.c. HS significantly decreased baseline T-core at 26 degreesC (36.5 +/- 0.1 degreesC) and increased counts of operant behaviour at 40degreesC (57 +/- 3) compared with results obtained following s.c. NS injection (37.4 +/- 0.1degreesC and 42 +/- 1, respectively). These responses to s.c. HS were inhibited by the intracerebroventricular injection of AT(1) (37.3 +/- 0.1 degreesC and 43 +/- 2, respectively; P &lt; 0.05) and V-1 antagonists (37.2 +/- 0.2&DEG;C and 42 +/- 2, respectively; P &lt; 0.05), although administration of both antagonists with s.c. NS had no effect. These results suggest that brain AII and AVP are involved in the decrease in T-core observed at neutral ambient temperature and the increase in heat-escape/cold-seeking behaviour in response to osmotic stimulation, via the central AT(1) and V-1 receptors, respectively.

To investigate the involvement of the periaqueductal gray (PAG) in the control of non-shivering thermogenesis, we tested the effects of electrical or chemical stimulation of the PAG on thermogenesis of brown adipose tissue (BAT) in urethane anesthetized rats. Electrical stimulation (0.1 mA, 33 Hz, 0.5 ms) or application of D,L-homocysteic acid (0.5 mM, 0.3 micro l) into the lateral region of the caudal PAG (cPAG) elicited BAT thermogenesis, measured as a rise in the local temperature of interscapular BAT. These results suggest that neurons in the cPAG send excitatory efferent signals for BAT thermogenesis.

To investigate the involvement of the periaqueductal gray (PAG) in the control of non-shivering thermogenesis, we tested the effects of electrical or chemical stimulation of the PAG on thermogenesis of brown adipose tissue (BAT) in urethane anesthetized rats. Electrical stimulation (0.1 mA, 33 Hz, 0.5 ms) or application of D,L-homocysteic acid (0.5 mM, 0.3 mul) into the lateral region of the caudal PAG (cPAG) elicited BAT thermogenesis, measured as a rise in the local temperature of interscapular BAT. These results suggest that neurons in the cPAG send excitatory efferent signals for BAT thermogenesis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Regional activation of the brain was studied in humans using functional magnetic resonance imaging during whole body cooling that produced thermal comfort/discomfort. Eight normal male subjects lay in a sleeping bag through which air was blown, exposing subjects to cold air (8 degrees C) for 22 min. Each subject scored their degree of thermal comfort and discomfort every min. As the subjects reported more discomfort the blood oxygen level dependent response in the bilateral amygdala increased. There was no activation in the thalamus, somatosensory, cingulate, or insula cortices. This result suggests that the amygdala plays a role in the genesis of thermal discomfort due to cold.

Regional activation of the brain was studied in humans using functional magnetic resonance imaging during whole body cooling that produced thermal comfort/discomfort. Eight normal male subjects lay in a sleeping bag through which air was blown, exposing subjects to cold air (8degreesC) for 22 min. Each subject scored their degree of thermal comfort and discomfort every min. As the subjects reported more discomfort the blood oxygen level dependent response in the bilateral amygdala increased. There was no activation in the thalamus, somatosensory, cingulate, or insula cortices. This result suggests that the amygdala plays a role in the genesis of thermal discomfort due to cold. (C) 2002 Published by Elsevier Science Ireland Ltd.

The preoptic area (POA) occupies a crucial position among the structures participating in thermoregulation, but we know little about its efferent projections for controlling various effector responses. In this study, we used an immunohistochemical analysis of Fos expression during local warming of the preoptic area. To avoid the effects of anesthesia or stress, which are known to elicit Fos induction in various brain regions, we used a novel thermode specifically designed for chronic warming of discrete brain structures in freely moving rats. At an ambient temperature of 22 degrees C, local POA warming increased Fos immunoreactivity in the supraoptic nucleus (SON) and the periaqueductal gray matter (PAG). Exposure of animals to an ambient temperature of 5 degrees C induced Fos immunoreactivity in the magnocellular paraventricular nucleus (mPVN) and the dorsomedial region of the hypothalamus (DMH). Concurrent warming of the POA suppressed Fos expression in these areas. These findings suggest that thermal information from the preoptic area sends excitatory signals to the SON and the PAG, and inhibitory signals to the mPVN and the DMH.

To investigate the involvement of the medullary raphé in thermoregulatory vasomotor control, we chemically manipulated raphé neuronal activity while monitoring the tail vasomotor response to preoptic warming. For comparison, neuronal activity in the rostral ventrolateral medulla (RVLM) was manipulated in similar experiments. Injections of D,L-homocysteic acid (DLH; 0.5 mM, 0.3 microl) into a restricted region of the ventral medullary raphé suppressed the tail vasodilatation normally elicited by warming the preoptic area to 42 degrees C. DLH injection into the RVLM also suppressed the vasodilatation elicited by preoptic warming. Injection of bicuculline (0.5 mM, 0.3 microl) into the same raphé region suppressed the vasodilatation elicited by preoptic warming. Bicuculline injection into the RVLM did not suppress tail vasodilatation. These results suggest that neurones in both the medullary raphé and the RVLM are vasoconstrictor to the tail, but only those in the raphé receive inhibitory input from the preoptic area. That input might be direct and/or indirect (e.g. via the periaqueductal grey matter).

To investigate the involvement of the medullary raphe in thermoregulatory vasomotor control, we chemically manipulated raphe neuronal activity while monitoring the tail vasomotor response to preoptic warming. For comparison, neuronal activity in the rostral ventrolateral medulla (RVLM) was manipulated in similar experiments. Injections Of D,L-homocysteic acid (DLH; 0.5 mm, 0.3 mul) into a restricted region of the ventral medullary raphe suppressed the tail vasodilatation normally elicited by warming the preoptic area to 42degreesC. DLH injection into the RVLM also suppressed the vasodilatation elicited by preoptic warming. Injection of bicuculline (0.5 mm, 0.3 mul) into the same raphe region suppressed the vasodilatation elicited by preoptic warming. Bicuculline injection into the RVLM did not suppress tail vasodilatation. These results suggest that neurones in both the medullary raphe and the RVLM are vasoconstrictor to the tail, but only those in the raphe receive inhibitory input from the preoptic area. That input might be direct and/or indirect (e.g. via the periaqueductal grey matter).

The preoptic area (POA) occupies a crucial position among the structures participating in thermoregulation, but we know little about its efferent projections for controlling various effector responses. In this study, we used an immunohistochemical analysis of Fos expression during local warming of the preoptic area. To avoid the effects of anesthesia or stress, which are known to elicit Fos induction in various brain regions, we used a novel thermode specifically designed for chronic warming of discrete brain structures in freely moving rats. At an ambient temperature of 22 degreesC, local POA warming increased Fos immunoreactivity in the supraoptic nucleus (SON) and the periaqueductal gray matter (PAG). Exposure of animals to an ambient temperature of 5 degreesC induced Fos immunoreactivity in the magnocellular paraventricular nucleus (mPVN) and the dorsomedial region of the hypothalamus (DMH). Concurrent warming of the POA suppressed Fos expression in these areas. These findings suggest that thermal information from the preoptic area sends excitatory signals to the SON and the PAG, and inhibitory signals to the mPVN and the DMH. (C) 2002 Elsevier Science BV All rights reserved.

We examined body core and skin temperatures and thermal comfort in young Japanese women suffering from unusual coldness (C, n = 6). They were selected by interview asking whether they often felt severe coldness even in an air-conditioned environment (20-26 degrees C) and compared with women not suffering from coldness (N, n = 6). Experiments were conducted twice for each subject: 120-min exposure at 23.5 degrees C or 29.5 degrees C after a 40-min baseline at 29.5 degrees C. Mean skin temperature decreased (P < 0.05) from 33.6 +/- 0.1 degrees C (mean +/- SE) to 31.1 +/- 0.1 degrees C and from 33.5 +/- 0.1 degrees C to 31.1 +/- 0.1 degrees C in C and N during the 23.5 degrees C exposure. Fingertip temperature in C decreased more than in N (P < 0.05; from 35.2 +/- 0.1 degrees C to 23.6 +/- 0.2 degrees C and from 35.5 +/- 0.1 degrees C to 25.6 +/- 0.6 degrees C). Those temperatures during the 29.5 degrees C exposure remained at the baseline levels. Rectal temperature during the 23.5 degrees C exposure was maintained at the baseline level in both groups (from 36.9 +/- 0.2 degrees C to 36.8 +/- 0.1 degrees C and 37.1 +/- 0.1 degrees C to 37.0 +/- 0.1 degrees C in C and N). The rating scores of cold discomfort for both the body and extremities were greater (P < 0.05) in C than in N. Thus the augmented thermal sensitivity of the body to cold and activated vasoconstriction of the extremities during cold exposure could be the mechanism for the severe coldness felt in C.

Recently we found that food-deprived rats kept under a light-dark cycle showed a progressive reduction in body temperature during the light phase on each subsequent day while body temperature in the dark phase did not differ from baseline values. In this study, we investigated the effect of lesioning the hypothalamic suprachiasmatic nucleus (SCN) on body temperature modulation by food deprivation. In the SCN-lesioned rats in which daily rhythms of body temperature and activity were abolished, body temperature was unchanged by food deprivation. We also examined the effect of food deprivation on the daily changes in Fos expression in the SCN. Under normal fed conditions the number of SCN cells expressing Fos is high during the day and low at night. Food deprivation attenuated the amplitude of this daily change in Fos expression in the SCN. This tendency was prominent in the dorsal part of the SCN, while the ventral part showed no effect of food deprivation. These findings suggest that the SCN plays some role in body temperature modulation due to food deprivation.

We examined body core and skin temperatures and thermal comfort in young Japanese women suffering from unusual coldness (C, n=6). They were selected by interview asking whether they often felt severe coldness even in an air-conditioned environment (20-26degreesC) and compared with women not suffering from coldness (N, n=6). Experiments were conducted twice for each subject: 120-min exposure at 23.5degreesC or 29.5degreesC after a 40-min baseline at 29.5degreesC. Mean skin temperature decreased (P&lt;0.05) from 33.6&PLUSMN;0.1&DEG;C (mean &PLUSMN; SE) to 31.1&PLUSMN;0.1&DEG;C and from 33.5&PLUSMN;0.1&DEG;C to 31.1&PLUSMN;0.1&DEG;C in C and N during the 23.5&DEG;C exposure. Fingertip temperature in C decreased more than in N (P&lt;0.05; from 35.2+/-0.1degreesC to 23.6+/-0.2degreesC and from 35.5+/-0.1degreesC to 25.6+/-0.6degreesC). Those temperatures during the 29.5degreesC exposure remained at the baseline levels. Rectal temperature during the 23.5degreesC exposure was maintained at the baseline level in both groups (from 36.9+/-0.2degreesC to 36.8+/-0.1degreesC and 37.1+/-0.1degreesC to 37.0+/-0.1degreesC in C and N). The rating scores of cold discomfort for both the body and extremities were greater (P&lt;0.05) in C than in N. Thus the augmented thermal sensitivity of the body to cold and activated vasoconstriction of the extremities during cold exposure could be the mechanism for the severe coldness felt in C.

Recently we found that food-deprived rats kept under a light-dark cycle showed a progressive reduction in body temperature during the light phase on each subsequent day while body temperature in the dark phase did not differ from baseline values. In this study, we investigated the effect of lesioning the hypothalamic suprachiasmatic nucleus (SCN) on body temperature modulation by food deprivation. In the SCN-lesioned rats in which daily rhythms of body temperature and activity were abolished, body temperature was unchanged by food deprivation. We also examined the effect of food deprivation on the daily changes in Fos expression in the SCN. Under normal fed conditions the number of SCN cells expressing Fos is high during the day and low at night. Food deprivation attenuated the amplitude of this daily change in Fos expression in the SCN. This tendency was prominent in the dorsal part of the SCN. while the ventral part showed no effect of food deprivation. These findings suggest that the SCN plays some role in body temperature modulation due to food deprivation. (C) 2002 Elsevier Science B.V. All rights reserved.

Although the posterior part of the hypothalamus has long, been considered important for thermoregulatory shivering, it is unknown whether the neurons there or the passing fibers are implicated in the response. Exposure of urethane-anesthetized rats to cold (15-21 degreesC) elicits shivering. An injection of muscimol (0.5 mm), a GABA(A) receptor agonist, into the medial part of the hypothalamus, including the dorsomedial and posterior nuclei, suppressed the cold-induced shivering. This result suggests that neurons having an excitatory effect on shivering are in this region of the hypothalamus.

We tested the hypothesis that renal tubular Na+ reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O-2 uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P&lt; 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na+ in the proximal tubules was higher in Ex than in C (P&lt; 0.05). Saline loading decreased fractional tubular reabsorption of Na+ from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P&lt; 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P&lt; 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na+ reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na+ reabsorption during saline infusion 24 h after exercise.

We tested the hypothesis that renal tubular Na+ reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O-2 uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P&lt; 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na+ in the proximal tubules was higher in Ex than in C (P&lt; 0.05). Saline loading decreased fractional tubular reabsorption of Na+ from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P&lt; 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P&lt; 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na+ reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na+ reabsorption during saline infusion 24 h after exercise.

We examined the effect of hypertonic saline injection on heat-escape/cold-seeking behavior in desalivated rats. Rats were exposed to 40 degreesC heat after normal (154 mM NaCl, control) or hypertonic saline (2,500 mM NaCl) injection (1 ml/100 g body wt). The rats received a 0 degreesC air for 30 s when they entered a specific area in an experimental box. Core temperature (T(c)) surpassed 40 degreesC in both conditions when 0 degreesC air was not available. Hypertonic saline injection produced a lower baseline T(c) than control [36.9 +/- 0.2 and 37.9 +/- 0.2 degreesC (means +/- SE), P &lt; 0.05] and a greater number of 0&lt;degrees&gt;C air rewards during the 2-h heat with lower T(c) at the end (48 +/- 1 and 34 +/- 2, 37.6 +/- 0.1, and 37.3 +/- 0.1 degreesC in the control and hypertonic saline injection trial, respectively, P &lt; 0.05, n = 6). However, T(c) was similar (37.7 +/- 0.2 and 37.6 +/- 0.4&lt;degrees&gt;C in the control and hypertonic saline injection trial, n = 5) when 0 degreesC air was automatically and intermittently (35 times) given during the heat. Rats augment heat-defense mechanisms in response to osmotic stress by lowering the baseline T(c) and increasing heat-escape/cold-seeking behavior.

We examined the effect of hypertonic saline injection on heat-escape/cold-seeking behavior in desalivated rats. Rats were exposed to 40 degreesC heat after normal (154 mM NaCl, control) or hypertonic saline (2,500 mM NaCl) injection (1 ml/100 g body wt). The rats received a 0 degreesC air for 30 s when they entered a specific area in an experimental box. Core temperature (T(c)) surpassed 40 degreesC in both conditions when 0 degreesC air was not available. Hypertonic saline injection produced a lower baseline T(c) than control [36.9 +/- 0.2 and 37.9 +/- 0.2 degreesC (means +/- SE), P &lt; 0.05] and a greater number of 0&lt;degrees&gt;C air rewards during the 2-h heat with lower T(c) at the end (48 +/- 1 and 34 +/- 2, 37.6 +/- 0.1, and 37.3 +/- 0.1 degreesC in the control and hypertonic saline injection trial, respectively, P &lt; 0.05, n = 6). However, T(c) was similar (37.7 +/- 0.2 and 37.6 +/- 0.4&lt;degrees&gt;C in the control and hypertonic saline injection trial, n = 5) when 0 degreesC air was automatically and intermittently (35 times) given during the heat. Rats augment heat-defense mechanisms in response to osmotic stress by lowering the baseline T(c) and increasing heat-escape/cold-seeking behavior.

The body temperature of homeothermic animals is regulated by systems that utilize multiple behavioral and autonomic effector responses. In the last few years, new approaches have brought us new information and new ideas about neuronal interconnections in the thermoregulatory network. Studies utilizing chemical stimulation of the preoptic area revealed both heat loss and production responses are controlled by warm-sensitive neurons. These neurons send excitatory efferent signals for the heat loss and inhibitory efferent signals for the heat production. The warm-sensitive neurons are separated and work independently to control these two opposing responses. Recent electrophysiological analysis have identified some neurons sending axons directly to the spinal cord for thermoregulatory effector control. Included are midbrain reticulospinal neurons for shivering and premotor neurons in the medulla oblongata for skin vasomotor control. As for the afferent side of the thermoregulatory network, the vagus nerve is recently paid much attention, which would convey signals for peripheral infection to the brain and be responsible for the induction of fever. The vagus nerve may also participate in thermoregulation in afebrile conditions, because some substances such as cholecyctokinin and leptin activate the vagus nerve. Although the functional role for this response is still obscure, the vagus may transfer nutritional and/or metabolic signals to the brain, affecting metabolism and body temperature. (C) 2000 Elsevier Science B.V. All rights reserved.

We tested the hypothesis that an elevation in albumin synthetic rate contributes to increased plasma albumin content during exercise-induced hypervolemia. Albumin synthetic rate was measured in seven healthy subjects at 1-5 and 21-22 h after 72 min of intense (85% peak oxygen consumption rate) intermittent exercise and after 5 h recovery in either upright (Up) or supine (Sup) postures. Deuterated phenylalanine (d(5)-Phe) was administrated by a primed-constant infusion method, and fractional synthetic rate (FSR) and absolute synthetic rate (ASR) of albumin were calculated from the enrichment of dB-Phe in plasma albumin, determined by gas chromatography-mass spectrometry. FSR of albumin in Up increased significantly (P &lt; 0.05) from 4.9 +/- 0.9%/day at control to 7.3 +/- 0.9%/day at 22 h of recovery. ASR of albumin increased from 87.9 +/- 17.0 to 141.1 +/- 16.6 mg albumin . kg body wt(-1) . day(-1). In contrast, FSR and ASR of albumin were unchanged in Sup (3.9 +/- 0.4 to 4.0 +/- 1.4%/day and 74.2 +/- 8.9 to 85.3 +/- 23.9 mg albumin . kg body wt(-1) . day(-1) at control and 22 h of recovery, respectively). Increased albumin synthesis after upright intense exercise contributes to the expansion of greater albumin content and its maintenance. We conclude that stimuli related to posture are critical in modulating the drive for albumin synthesis after intense exercise.

We examined the hypothesis that activation of the muscle metaboreflex during dynamic exercise would augment influences tending to cause a rise in arginine vasopressin, plasma renin activity, and catecholamines during dynamic exercise in humans. Ten healthy adults performed 30 min of supine cycle ergometer exercise at similar to 50% of peak oxygen consumption with or without moderate muscle metaboreflex activation by application of 35 mmHg lower body positive pressure (LBPP). Application of LBPP during the first 15 or last 15 min of exercise increased mean arterial blood pressure, plasma lactate concentration, and minute ventilation, indicating an activation of the muscle metaboreflex. These changes were rapidly reversed when LBPP was removed. During exercise at this intensity, LBPP augmented the release of arginine vasopressin and catecholamines but not of plasma renin activity. These results suggest that, although in humans hormonal. responses are induced by moderate activation of the muscle metaboreflex during dynamic exercise, the thresholds for these responses may not be uniform among the various glands and hormones.

We tested the hypothesis that an elevation in albumin synthetic rate contributes to increased plasma albumin content during exercise-induced hypervolemia. Albumin synthetic rate was measured in seven healthy subjects at 1-5 and 21-22 h after 72 min of intense (85% peak oxygen consumption rate) intermittent exercise and after 5 h recovery in either upright (Up) or supine (Sup) postures. Deuterated phenylalanine (d(5)-Phe) was administrated by a primed-constant infusion method, and fractional synthetic rate (FSR) and absolute synthetic rate (ASR) of albumin were calculated from the enrichment of dB-Phe in plasma albumin, determined by gas chromatography-mass spectrometry. FSR of albumin in Up increased significantly (P &lt; 0.05) from 4.9 +/- 0.9%/day at control to 7.3 +/- 0.9%/day at 22 h of recovery. ASR of albumin increased from 87.9 +/- 17.0 to 141.1 +/- 16.6 mg albumin . kg body wt(-1) . day(-1). In contrast, FSR and ASR of albumin were unchanged in Sup (3.9 +/- 0.4 to 4.0 +/- 1.4%/day and 74.2 +/- 8.9 to 85.3 +/- 23.9 mg albumin . kg body wt(-1) . day(-1) at control and 22 h of recovery, respectively). Increased albumin synthesis after upright intense exercise contributes to the expansion of greater albumin content and its maintenance. We conclude that stimuli related to posture are critical in modulating the drive for albumin synthesis after intense exercise.

We examined the hypothesis that activation of the muscle metaboreflex during dynamic exercise would augment influences tending to cause a rise in arginine vasopressin, plasma renin activity, and catecholamines during dynamic exercise in humans. Ten healthy adults performed 30 min of supine cycle ergometer exercise at similar to 50% of peak oxygen consumption with or without moderate muscle metaboreflex activation by application of 35 mmHg lower body positive pressure (LBPP). Application of LBPP during the first 15 or last 15 min of exercise increased mean arterial blood pressure, plasma lactate concentration, and minute ventilation, indicating an activation of the muscle metaboreflex. These changes were rapidly reversed when LBPP was removed. During exercise at this intensity, LBPP augmented the release of arginine vasopressin and catecholamines but not of plasma renin activity. These results suggest that, although in humans hormonal. responses are induced by moderate activation of the muscle metaboreflex during dynamic exercise, the thresholds for these responses may not be uniform among the various glands and hormones.

To clarify whether an increase in urinary sodium (Na) excretion during cold-air exposure is attenuated in trained athletes, we analyzed the urinary and hormonal responses to cold-air exposure at 15 degrees C in trained (TR, n=9) and untrained men (UT, n=9), During 15 degrees C exposure in the UT group, the urinary Na excretion (UNaV), fractional excretion of Na and urinary Na to K ratio (U-Na/K) increased significantly (p&lt;0.01-0.05), but there were no variations in creatinine clearance or the filtered Na load. In the TR group, however, no significant changes were demonstrated in these parameters. The amount of increase in plasma noradrenaline and of decrease in plasma volume were greater, and the ADH and adrenaline responses were smaller in the TR group than those found in the UT group during 15 degrees C air exposure. A significant positive correlation was demonstrated between the increase of UNaV and both the relative changes of U-Na/K and mean blood pressure. These results indicated that natriuresis during cold-air exposure was induced by the decrease in tubular reabsorption of Na, and that natriuresis was attenuated in trained athletes.

To test the hypothesis that exercise-induced hypervolemia is a posture-dependent process, we measured plasma volume, plasma albumin content, and renal function in seven healthy subjects for 22 h after single upright (Up) or supine (Sup) intense (85% peak oxygen consumption rate) exercise. This posture was maintained for 5 h after exercise. Plasma volume decreased during exercise but returned to control levels by 5 h of recovery in both postures. By 22 h of recovery, plasma volume increased 2.4 +/- 0.8 ml/kg in Up but decreased 2.1 +/- 0.8 ml/kg in Sup. The plasma volume expansion in Up was accompanied by an increase in plasma albumin content (0.11 +/- 0.04 g/kg; P &lt; 0.05). Plasma albumin content was unchanged in Sup. Urine volume and sodium clearance were lower in Up than Sup (P &lt; 0.05) by 5 h of recovery. These data suggest that increased plasma albumin content contributes to the acute phase of exercise-induced hypervolemia. More importantly, the mechanism by which exercise influences the distribution of albumin between extra- and intravascular stores after exercise is altered by posture and is unknown. We speculate that factors associated with postural changes (e.g., central venous pressure) modify the increase in plasma albumin content and the plasma volume expansion after exercise.

To test the hypothesis that exercise-induced hypervolemia is a posture-dependent process, we measured plasma volume, plasma albumin content, and renal function in seven healthy subjects for 22 h after single upright (Up) or supine (Sup) intense (85% peak oxygen consumption rate) exercise. This posture was maintained for 5 h after exercise. Plasma volume decreased during exercise but returned to control levels by 5 h of recovery in both postures. By 22 h of recovery, plasma volume increased 2.4 +/- 0.8 ml/kg in Up but decreased 2.1 +/- 0.8 ml/kg in Sup. The plasma volume expansion in Up was accompanied by an increase in plasma albumin content (0.11 +/- 0.04 g/kg; P &lt; 0.05). Plasma albumin content was unchanged in Sup. Urine volume and sodium clearance were lower in Up than Sup (P &lt; 0.05) by 5 h of recovery. These data suggest that increased plasma albumin content contributes to the acute phase of exercise-induced hypervolemia. More importantly, the mechanism by which exercise influences the distribution of albumin between extra- and intravascular stores after exercise is altered by posture and is unknown. We speculate that factors associated with postural changes (e.g., central venous pressure) modify the increase in plasma albumin content and the plasma volume expansion after exercise.

The impact of posture on the immediate recovery of intravascular fluid and protein after intense exercise was determined in 14 volunteers. Forces which govern fluid and protein movement in muscle interstitial fluid pressure (P-ISF), interstitial colloid osmotic pressure (COPi), and plasma colloid osmotic pressure (COPi) were measured before and after exercise in the supine or upright position. During exercise, plasma volume (PV) decreased by 5.7 +/- 0.7 and 7.0 +/- 0.5 ml/kg body weight in the supine and upright posture, respectively. During recovery, PV returned to its baseline value within 30 min regardless of posture. PV fell below this level by 60 and 120 min in the supine and upright posture, respectively (P &lt; 0.05). Maintenance of PV in the upright position was associated with a decrease in systolic blood pressure, an increase in COPp (from 25 +/- 1 to 27 +/- 1 mmHg; P &lt; 0.05), and an increase in P-ISF (from 5 +/- 1 to 6 +/-: 2 mmHg), whereas COPi was unchanged. Increased PISF indicates that the hydrostatic pressure gradient favors fluid movement into the vascular space. However, retention of the recaptured fluid in the plasma is promoted only in the upright posture because of increased COPi.

The impact of posture on the immediate recovery of intravascular fluid and protein after intense exercise was determined in 14 volunteers. Forces which govern fluid and protein movement in muscle interstitial fluid pressure (P-ISF), interstitial colloid osmotic pressure (COPi), and plasma colloid osmotic pressure (COPi) were measured before and after exercise in the supine or upright position. During exercise, plasma volume (PV) decreased by 5.7 +/- 0.7 and 7.0 +/- 0.5 ml/kg body weight in the supine and upright posture, respectively. During recovery, PV returned to its baseline value within 30 min regardless of posture. PV fell below this level by 60 and 120 min in the supine and upright posture, respectively (P &lt; 0.05). Maintenance of PV in the upright position was associated with a decrease in systolic blood pressure, an increase in COPp (from 25 +/- 1 to 27 +/- 1 mmHg; P &lt; 0.05), and an increase in P-ISF (from 5 +/- 1 to 6 +/-: 2 mmHg), whereas COPi was unchanged. Increased PISF indicates that the hydrostatic pressure gradient favors fluid movement into the vascular space. However, retention of the recaptured fluid in the plasma is promoted only in the upright posture because of increased COPi.

We tested the hypothesis that cardiovascular responses to lower body positive pressure (LBPP) would be dependent on the posture of the subject and also on the background condition (rest or exercise). We measured heart rate (HR), mean arterial blood pressure (MAP), and cardiac stroke volume in eight subjects at rest and during cycle ergometer exercise (76 +/- 3 W) with and without LBPP (25, 50, and 75 mmHg) in the supine and upright positions. At rest, the increase in MAP was proportional to the increase in LBPP and was greater in the supine (6 +/- 2, 15 +/- 3, and 26 +/- 3 mmHg) than in the upright (2 +/- 3, 9 +/- 3, and 17 +/- 3 mmHg) position. During dynamic exercise, the increases in MAP evoked by 25, 50, and 75 mmHg LBPP were greater in the supine (13 +/- 2, 28 +/- 3, and 40 +/- 3 mmHg) than in the upright (7 +/- 3, 12 +/- 3, and 25 +/- 3 mmHg) position. We conclude that the systemic pressure response to LBPP is clearly dependent on the body position, with the larger pressure responses being associated with the supine position both at rest and during dynamic leg exercise.

To elucidate the role of increased plasma osmolality (P-osmol), which occurs during exercise in the regulation of cutaneous vasodilation (CVD) during exercise, we determined the relationship between the change in esophageal temperature (Delta T-es) required to elicit CVD (Delta T-es threshold for CVD) and P-osmol during light and moderate exercise (30 and 55% of peak oxygen consumption, respectively) and passive body heating. Then we compared the relationship with the data obtained in our previous study [A. Takamata, K. Nagashima, H. Nose, and T. Morimoto.Am. J. Physiol. 273 (Regulatory Integrative Comp. Physiol. 42): R197-R204, 1997], in which we determined the relationships during passive body heating following isotonic (0.9% NaCl) or hypertonic (2 or 3% NaCl) saline infusions in the same subjects. P-osmol values at 5 min after the onset of exercise were 287.5 +/- 0.9 mosmol/kgH(2)O during light exercise and 293.0 +/- 1.2 mosmol/kgH(2)O during moderate exercise. P-osmol just before passive body heating was 289.9 +/- 1.4 mosmol/kgH(2)O. The Delta T-es threshold for CVD was 0.09 +/- 0.05 degrees C during light exercise, 0.31 +/- 0.09 degrees C during moderate exercise, and 0.10 +/- 0.05 degrees C during passive body heating. The relationship between the Delta T-es threshold for CVD and P-osmol was shown to be on the same regression line both during exercise and during passive body heating with or without infusions [A. Takamata, K. Nagashima, H. Nose, and T. Morimoto. Am. J. Physiol. 273 (Regulatory Integrative Comp. Physiol. 42): R197-R204, 1997]. Our data suggest that the elevated body core temperature threshold for CVD during exercise could be the result of increased P-osmol induced by exercise and is not due to reduced plasma volume or the intensity of the exercise itself.

To elucidate the role of increased plasma osmolality (P-osmol), which occurs during exercise in the regulation of cutaneous vasodilation (CVD) during exercise, we determined the relationship between the change in esophageal temperature (Delta T-es) required to elicit CVD (Delta T-es threshold for CVD) and P-osmol during light and moderate exercise (30 and 55% of peak oxygen consumption, respectively) and passive body heating. Then we compared the relationship with the data obtained in our previous study [A. Takamata, K. Nagashima, H. Nose, and T. Morimoto.Am. J. Physiol. 273 (Regulatory Integrative Comp. Physiol. 42): R197-R204, 1997], in which we determined the relationships during passive body heating following isotonic (0.9% NaCl) or hypertonic (2 or 3% NaCl) saline infusions in the same subjects. P-osmol values at 5 min after the onset of exercise were 287.5 +/- 0.9 mosmol/kgH(2)O during light exercise and 293.0 +/- 1.2 mosmol/kgH(2)O during moderate exercise. P-osmol just before passive body heating was 289.9 +/- 1.4 mosmol/kgH(2)O. The Delta T-es threshold for CVD was 0.09 +/- 0.05 degrees C during light exercise, 0.31 +/- 0.09 degrees C during moderate exercise, and 0.10 +/- 0.05 degrees C during passive body heating. The relationship between the Delta T-es threshold for CVD and P-osmol was shown to be on the same regression line both during exercise and during passive body heating with or without infusions [A. Takamata, K. Nagashima, H. Nose, and T. Morimoto. Am. J. Physiol. 273 (Regulatory Integrative Comp. Physiol. 42): R197-R204, 1997]. Our data suggest that the elevated body core temperature threshold for CVD during exercise could be the result of increased P-osmol induced by exercise and is not due to reduced plasma volume or the intensity of the exercise itself.

We tested the hypothesis that cardiovascular responses to lower body positive pressure (LBPP) would be dependent on the posture of the subject and also on the background condition (rest or exercise). We measured heart rate (HR), mean arterial blood pressure (MAP), and cardiac stroke volume in eight subjects at rest and during cycle ergometer exercise (76 +/- 3 W) with and without LBPP (25, 50, and 75 mmHg) in the supine and upright positions. At rest, the increase in MAP was proportional to the increase in LBPP and was greater in the supine (6 +/- 2, 15 +/- 3, and 26 +/- 3 mmHg) than in the upright (2 +/- 3, 9 +/- 3, and 17 +/- 3 mmHg) position. During dynamic exercise, the increases in MAP evoked by 25, 50, and 75 mmHg LBPP were greater in the supine (13 +/- 2, 28 +/- 3, and 40 +/- 3 mmHg) than in the upright (7 +/- 3, 12 +/- 3, and 25 +/- 3 mmHg) position. We conclude that the systemic pressure response to LBPP is clearly dependent on the body position, with the larger pressure responses being associated with the supine position both at rest and during dynamic leg exercise.

To assess the impact of continuous negative-pressure breathing (CNPB) on the regulation of skin blood flow, we measured forearm blood flow (FBF) by venous-occlusion plethysmography and laser-Doppler flow (LDF) at the anterior chest during exercise in a hot environment (ambient temperature = 30 degrees C, relative humidity = similar to 30%). Seven male subjects exercised in the upright position at an intensity of 60% peak oxygen consumption rate for 40 min with and without CNPB after 20 min of exercise. The esophageal temperature (T-es) in both conditions increased to 38.1 degrees C by the end of exercise, without any significant differences between the two trials. Mean arterial pressure (MAP) increased by similar to 15 mmHg by 8 min of exercise, without any significant difference between the two trials before CNPB. However, CNPB reduced MAP by similar to 10 mmHg after 24 min of exercise (P &lt; 0.05). The increase in FBF and LDF in the control condition leveled off after 18 min of exercise above a T-es of 37.7 degrees C, whereas in the CNPB trial the increase continued, with a rise in T-es despite the decrease in MAP. These results suggest that CNPB enhances vasodilation of skin above a T-es of similar to 38 degrees C by stretching intrathoracic baroreceptors such as cardiopulmonary baroreceptors.

To assess the impact of continuous negative-pressure breathing (CNPB) on the regulation of skin blood flow, we measured forearm blood flow (FBF) by venous-occlusion plethysmography and laser-Doppler flow (LDF) at the anterior chest during exercise in a hot environment (ambient temperature = 30 degrees C, relative humidity = similar to 30%). Seven male subjects exercised in the upright position at an intensity of 60% peak oxygen consumption rate for 40 min with and without CNPB after 20 min of exercise. The esophageal temperature (T-es) in both conditions increased to 38.1 degrees C by the end of exercise, without any significant differences between the two trials. Mean arterial pressure (MAP) increased by similar to 15 mmHg by 8 min of exercise, without any significant difference between the two trials before CNPB. However, CNPB reduced MAP by similar to 10 mmHg after 24 min of exercise (P &lt; 0.05). The increase in FBF and LDF in the control condition leveled off after 18 min of exercise above a T-es of 37.7 degrees C, whereas in the CNPB trial the increase continued, with a rise in T-es despite the decrease in MAP. These results suggest that CNPB enhances vasodilation of skin above a T-es of similar to 38 degrees C by stretching intrathoracic baroreceptors such as cardiopulmonary baroreceptors.

We studied the difference of thermoregulatory responses between trained male athletes (TR, n = 9) and untrained men (UT, n = 7) during 60 min of cold exposure (15 degrees C) without shivering, and examined the effects of physical fitness and body fat on these responses. Mean skin temperature ((T) over bar(sk)), esophageal temperature (T-es), and skin conductance (K-b) were similar between TR and UT, and heat production ((M) over bar) for TR increased significantly during exposure at 15 degrees C. The (M) over bar at 15 degrees C correlated positively with maximal oxygen uptake and negatively with body fat (%BF), but not with T-es. The K-b correlated negatively with T-es and positively with (T) over bar(sk).The %BF also correlated negatively with K-b and (T) over bar(sk) during exposure at 15 degrees C, and the slope of %BF vs. (T) over bar(sk) relationship was significantly steeper in TR than in UT. These results suggest that (1) body temperature is maintained by the reduction of skin conductance, and (2) heat insulation independent of body fat is enhanced in trained athletes during cold exposure without shivering.

To test the hypotheses that plasma volume (PV) expansion 24 h after intense exercise is associated with reduced transcapillary escape rate of albumin (TERalb) and that local changes in transcapillary forces in the previously active tissues favor retention of protein in the vascular space, we measured PV, TERalb, plasma colloid osmotic pressure (COPp), interstitial fluid hydrostatic pressure (Pi), and colloid osmotic pressure in leg muscle and skin and capillary filtration coefficient (CFC) in the arm and leg in seven men and women before and 24 h after intense upright cycle ergometer exercise. Exercise expanded PV by 6.4% at 24 h (43.9 +/- 0.8 to 46.8 +/- 1.2 ml/kg, P &lt; 0.05) and decreased total protein concentration (6.5 +/- 0.1 to 6.3 +/- 0.1 g/dl, P &lt; 0.05) and COPp (26.1 +/- 0.8 to 24.3 +/- 0.9 mmHg, P &lt; 0.05), although plasma albumin concentration was unchanged. TERalb tended to decline (8.4 +/- 0.5 to 6.5 +/- 0.7%/h, P = 0.11) and was correlated with the increase in PV (r = -0.69, P &lt; 0.05). CFC increased in the leg (3.2 +/- 0.2 to 4.3 +/- 0.5 mu l.100 g(-1).min(-1).mmHg(-1), P &lt; 0.05), and Pi showed a trend to increase in the leg muscle (2.8 +/- 0.7 to 3.8 +/- 0.3 mmHg, P = 0.08). These data demonstrate that TERalb is associated with PV regulation and that local transcapillary forces in the leg muscle may favor retention of albumin in the vascular space after exercise.

To test the hypotheses that plasma volume (PV) expansion 24 h after intense exercise is associated with reduced transcapillary escape rate of albumin (TERalb) and that local changes in transcapillary forces in the previously active tissues favor retention of protein in the vascular space, we measured PV, TERalb, plasma colloid osmotic pressure (COPp), interstitial fluid hydrostatic pressure (Pi), and colloid osmotic pressure in leg muscle and skin and capillary filtration coefficient (CFC) in the arm and leg in seven men and women before and 24 h after intense upright cycle ergometer exercise. Exercise expanded PV by 6.4% at 24 h (43.9 +/- 0.8 to 46.8 +/- 1.2 ml/kg, P &lt; 0.05) and decreased total protein concentration (6.5 +/- 0.1 to 6.3 +/- 0.1 g/dl, P &lt; 0.05) and COPp (26.1 +/- 0.8 to 24.3 +/- 0.9 mmHg, P &lt; 0.05), although plasma albumin concentration was unchanged. TERalb tended to decline (8.4 +/- 0.5 to 6.5 +/- 0.7%/h, P = 0.11) and was correlated with the increase in PV (r = -0.69, P &lt; 0.05). CFC increased in the leg (3.2 +/- 0.2 to 4.3 +/- 0.5 mu l.100 g(-1).min(-1).mmHg(-1), P &lt; 0.05), and Pi showed a trend to increase in the leg muscle (2.8 +/- 0.7 to 3.8 +/- 0.3 mmHg, P = 0.08). These data demonstrate that TERalb is associated with PV regulation and that local transcapillary forces in the leg muscle may favor retention of albumin in the vascular space after exercise.

We examined the effect of increased plasma osmolality (P-osm) on cutaneous vasodilatory response to increased esophageal temperature (T-es) in passively heated human subjects (n = 6). To modify P-osm, subjects were infused with 0.9, 2, or 3% NaCl infusions (Inf) for 90 min on separate days. Infusion rates were 0.2, 0.15, and 0.125 ml . min(-1). kg body wt(-1) for 0.9, 2, and 3% Inf, respectively, which produced relatively similar plasma volume expansion. Thirty minutes after the end of infusion, subjects immersed their lower legs in a water bath at 42 degrees C (room temperature 28 degrees C) for 60 min after 10 min of preheating control measurements. Passive heating without infusion (NI) served as time control to account for the effect of volume expansion. P-osm (mosmol/kgH(2)O) values at the onset of passive heating were 289.9 +/- 1.4, 292.1 +/- 0.6, 298.7 +/- 0.7, and 305.6 +/- 0.6 after NI, 0.9% Inf, 2% Inf, and 3% Inf, respectively. The increases in T-es (Delta T-es) at equilibrium during passive heating (mean Delta T-es during 55-60 min) were 0.47 +/- 0.08, 0.59 +/- 0.08, 0.85 +/- 0.13, and 1.09 +/- 0.12 degrees C after NI, 0.9% Inf, 2% Inf, and 3% Inf, respectively, which indicates that T-es at equilibrium increased linearly as P-osm increased. Delta T-es required to elicit cutaneous vasodilation (Delta T-es threshold for cutaneous vasodilation) also increased linearly as P-osm increased as well as the Delta T-es threshold for sweating. The calculated increases in these thresholds per unit rise in P-osm from regression analysis were 0.044 degrees C for the cutaneous vasodilation and 0.034 degrees C for sweating. Thus the Delta T-es thresholds for cutaneous vasodilation and sweating are shifted to higher Delta T-es along with the increase in P-osm, and these shifts resulted in the higher increase in T-es during passive heating.

To clarify the relationship between aerobic power ((V) over dot O-2max), blood volume (BV), and thermoregulatory responses to exercise-heat stress, we analyzed the cross-sectional relationship between the resting BV, plasma volume (PV), erythrocyte volume (EV), (V) over dot O-2max, forearm blood flow (FBF), and sweating responses during exercise in a hot environment (31 degrees C, 50% relative humidity). Twelve college-aged male subjects with a mean maximal oxygen uptake of 48 (range 42-59) mL.kg(-1).min(-1), a mean PV of 54 (range 42-72) mL.kg(-1), a mean EV of 31 (range 23-43) mL.kg(-1), and a mean BV of 85 (range 67-115) mL.kg(-1) (measured by the Evans Blue dye dilution method) performed three sessions of 20-min cycle exercise at two levels of intensity (40% and 60% (V) over dot O-2max). The BV, PV, and EV correlated positively with peak FBF (r = 0.596-0.711, P &lt; 0.05), the increase of FBF in response to a unit rise in esophageal temperature (Tes; peak Delta FBF/peak Delta Tes) (r = 0.592-0.656, P &lt; 0.05) and with total sweat loss (TSL) (r = 0.599-0.634, P &lt; 0.05) during the exercise. The (V) over dot O-2max correlated with TSL during exercise at 40% (V) over dot O-2max (r = 0.578, P &lt; 0.05), but not with peak FBF and peak Delta FBF/peak Delta Tes. The (V) over dot O-2max per lean body mass also showed a significant positive correlation with BV (r = 0.769, P &lt; 0.01), PV (r = 0.706, P &lt; 0.05), and with EV (r = 0.841, P &lt; 0.001). The peak Delta FBF/peak Delta Tes was correlated positively with peak FBF (r = 0.597-0.830, P &lt; 0.05-0.01) and negatively with peak Tes (r = 0.641-0.769, P &lt; 0.05-0.01) during the exercise at the two levels. However, the chest sweat rate (CSR), TSL, and the increase of CSR in response to a unit rise in Tes (peak Delta CSR/peak Delta Tes) showed no correlation with peak Tes during the exercise at the two levels. These findings suggest that 1) heat dissipation responses during exercise were related more to blood volume than aerobic power and 2) skin blood flow was related more to body temperature than sweating responses during exercise under mild heat stress.

We examined the effect of increased plasma osmolality (P-osm) on cutaneous vasodilatory response to increased esophageal temperature (T-es) in passively heated human subjects (n = 6). To modify P-osm, subjects were infused with 0.9, 2, or 3% NaCl infusions (Inf) for 90 min on separate days. Infusion rates were 0.2, 0.15, and 0.125 ml . min(-1). kg body wt(-1) for 0.9, 2, and 3% Inf, respectively, which produced relatively similar plasma volume expansion. Thirty minutes after the end of infusion, subjects immersed their lower legs in a water bath at 42 degrees C (room temperature 28 degrees C) for 60 min after 10 min of preheating control measurements. Passive heating without infusion (NI) served as time control to account for the effect of volume expansion. P-osm (mosmol/kgH(2)O) values at the onset of passive heating were 289.9 +/- 1.4, 292.1 +/- 0.6, 298.7 +/- 0.7, and 305.6 +/- 0.6 after NI, 0.9% Inf, 2% Inf, and 3% Inf, respectively. The increases in T-es (Delta T-es) at equilibrium during passive heating (mean Delta T-es during 55-60 min) were 0.47 +/- 0.08, 0.59 +/- 0.08, 0.85 +/- 0.13, and 1.09 +/- 0.12 degrees C after NI, 0.9% Inf, 2% Inf, and 3% Inf, respectively, which indicates that T-es at equilibrium increased linearly as P-osm increased. Delta T-es required to elicit cutaneous vasodilation (Delta T-es threshold for cutaneous vasodilation) also increased linearly as P-osm increased as well as the Delta T-es threshold for sweating. The calculated increases in these thresholds per unit rise in P-osm from regression analysis were 0.044 degrees C for the cutaneous vasodilation and 0.034 degrees C for sweating. Thus the Delta T-es thresholds for cutaneous vasodilation and sweating are shifted to higher Delta T-es along with the increase in P-osm, and these shifts resulted in the higher increase in T-es during passive heating.

To assess the relationship between atrial natriuretic peptide (ANP) and the reduction in plasma volume (PV) during exercise, we measured changes in PV and ANP in seven male volunteers during treadmill exercise in air (AE) and with water immersion (WE) together with time control studies of rest in air and in water. Blood samples were collected from a catheter in the antecubital vein at exercise intensities of 32, 49, 65, and 78% of peak oxygen consumption (Vo(2)). Plasma ANP in AE increased significantly from the resting value [15 +/- 1 (SE) pg/ml] only at 78% of peak Vo(2) (29 +/- 5 pg/ml), whereas ANP in WE increased significantly at exercise levels of &gt;49% of peak Vo(2) and reached 68 +/- 9 pg/ml at 78% of peak Vo(2). Although PV in AE and WE decreased significantly with Vo(2) of &gt; 49% of peak Vo(2) (P &lt; 0.01), the decrease from the resting value in WE was significantly greater than that in AE of &gt;65% of peak Vo(2) (P &lt; 0.01) and the decreases at 78% of peak Vo(2) were -9.7 +/- 0.8 and -6.1 +/- 1.7%, respectively. The difference in the decrease in PV between AE and WE at corresponding Vo(2) correlated strongly with that in the increase in ANP (r = -0.97; P &lt; 0.01). These results are consistent with the hypothesis that ANP may be involved in the fluid shift from the intra- to extravascular space during exercise.

To assess the effects of alpha-adrenergic activation on hemorrhage-induced shifts of K+, Na+ and fluid between the intravascular and extravascular spaces, we continuously measured changes in plasma concentrations of K+ and Na+ (Delta[K+]p, Delta[Na+]p) and blood volume (Delta BV) over 60 min after hemorrhage in nephrectomized rats. Hemorrhage was conducted over 5 min at the level of 0.5, 1.0 and 1.5% of body weight (H-0.5, H-1.0, H-1.5), and the result was compared with hemorrhage of 1.0% body weight after administration of alpha(1)-adrenoreceptor antagonist prazosin (0.2 mg/kg, H-1.0P). Delta[K+]p increased significantly (p &lt; 0.05) after hemorrhage, and the peak value was proportional to the level of hemorrhage (0.18 +/- 0.08, 0.62 +/- 0.22 and 1.64 +/- 0.19 meq/l in H-0.5, H-1.0 and H-1.5, respectively). Delta[Na+]p decreased significantly (p &lt; 0.05) after hemorrhage, and the decrease was sustained until the end of the experiment (-0.8 +/- 0.6, -1.0 +/- 0.5 and -2.2 +/- 0.5 meq/l in H-0.5, H-1.0 and H-1.5, respectively). In H-1.0P, the increase in Delta[K+]p (0.25 +/- 0.09 meq/l at the peak) and the decrease in Delta[Na+]p (-0.2 +/- 0.1 meq/l at the bottom) were suppressed significantly (p &lt; 0.05) compared to H-1.0. Although Delta BV was greater in H-1.0P than H-1.0, plasma K+ content was not different between the groups. In H-1.0, the calculated concentrations of K+ and Na+ in the fluid which shifted into the intravascular space ([K+]sf, [Na+]sf) in the first 30 min after hemorrhage were higher in [K+]sf (6.25 +/- 0.70 meq/l) and lower in [Na+]sf (128.0 +/- 3.2 meq/l) than the pre-hemorrhage plasma level. With regard to H-1.0P, [K+]sf and [Na+]sf were not different from the pre-hemorrhage level of plasma. These results suggest that alpha-adrenergic activation after hemorrhage induces K+ movement into plasma to increase [K+]p, which might be related to the fluid shift from the intracellular to the extracellular space.

To assess the relationship between atrial natriuretic peptide (ANP) and the reduction in plasma volume (PV) during exercise, we measured changes in PV and ANP in seven male volunteers during treadmill exercise in air (AE) and with water immersion (WE) together with time control studies of rest in air and in water. Blood samples were collected from a catheter in the antecubital vein at exercise intensities of 32, 49, 65, and 78% of peak oxygen consumption (Vo(2)). Plasma ANP in AE increased significantly from the resting value [15 +/- 1 (SE) pg/ml] only at 78% of peak Vo(2) (29 +/- 5 pg/ml), whereas ANP in WE increased significantly at exercise levels of &gt;49% of peak Vo(2) and reached 68 +/- 9 pg/ml at 78% of peak Vo(2). Although PV in AE and WE decreased significantly with Vo(2) of &gt; 49% of peak Vo(2) (P &lt; 0.01), the decrease from the resting value in WE was significantly greater than that in AE of &gt;65% of peak Vo(2) (P &lt; 0.01) and the decreases at 78% of peak Vo(2) were -9.7 +/- 0.8 and -6.1 +/- 1.7%, respectively. The difference in the decrease in PV between AE and WE at corresponding Vo(2) correlated strongly with that in the increase in ANP (r = -0.97; P &lt; 0.01). These results are consistent with the hypothesis that ANP may be involved in the fluid shift from the intra- to extravascular space during exercise.

&emsp;This study was designed to clarify the accuracy of X-band multi-parameter radar (X-MP) over the Hokuriku region using rain gauge data and quantitative precipitation estimation (QPE) by C-band radar. Moreover, this study used results of the correlation coefficient and estimate error for QPE accuracy analysis.<br>&emsp;Temporal analysis revealed that X-MPs provide observation data with high accuracy for short-term downpours, but results for long-term and light rainfall or regions distant from the radar site were less accurate.<br>&emsp;Spatial analysis showed the X-MP data accuracy was observable with sufficient accuracy within a range of 2.25 × 2.25 km as the center of each rain gauge station. The X-MP data accuracy has less than the C-band radar data accuracy beyond a 20 km radius from the radar site.<br>&emsp;Quantitative analysis of the rainy season and snowy season, total precipitation of X-MP and C-band radar were overestimated from that of the rain gauge station, it was especially overestimated significantly during the snowy season.

The purpose of this study is to clarify the characteristics of observed polarization parameter by X-band MP radar (X-MP) over Hokuriku region. Especially, this study analyzed the raindrop size distribution (DSD) using observed horizontal polarization Zh, measured differential reflectivity ZDR and specific differential phase shift KDP as polarization parameter. As a result of analysis of observed polarization parameter, ZDR and Zh have liner relation by heavy rainfall, and ZDR and Zh may be formulated raindrop and snowflake by snowfall and graupel. Precipitation intensity R and ZDR have correlation relation by heavy rainfall, however snowfall haven&rsquo;t that, especially same value of ZDR have widely distributed R by snowfall.

＜Key Points＞(1)恒温動物は、生命活動に必要な高い基礎代謝のために体温の異常が起こった際には、脆弱な動物であるといえる。(2)概日リズム、食事、性周期などによりヒトの体温は変動するが、多くの場合1℃以内にとどまっている。(3)高体温症、低体温症などの体温異常の原因は多くあるが、急性かつ平温からの変動が大きくなるのは暑熱、寒冷などの環境因子が大きい。(4)小児は自律性体温調節が未発達であるが、体温調節異常が起こる原因としてむしろ着衣、エアコンをつけたりする行動性体温調節ができないことが大きい。(5)高体温症と発熱は明確に区別される。(著者抄録)

The purpose of this study was to examine the physiological and psychological responses to color lights during cold water immersion test. Ten female subjects aged between 20 to 30 years were asked to immerse their left hand in 15℃ water for 3 minutes respectively under white, blue and red color light. The subjects&#039; skin temperature, skin blood flow, blood pressure and electrocardiogram were continuously measured. At the meantime, psychological questionnaires were conducted, focusing on subjects&#039; impression of the color lights, mood, thermesthesia, cold discomfort, and subjective feelings of temperature recovery during the test. The physiological results indicate that under blue color light, reduced skin temperature under cold water immersion recovered relatively faster compared to other color lights. Skin blood flow also recovered faster under blue color light. The psychological results show difference in the impression among 3 color lights in terms of &quot;pleasant&quot; and &quot;warm and cool&quot;. Meanwhile, subjects&#039; mood and thermesthesia were different to each color lights. Specifically, blue color light, evaluated as cool color was considered increasing the discomfort of cold, thus leading to emotional arousal. On the other hand, red color light, evaluated as warm color was considered decreasing the discomfort of cold. In this study, as the characteristic of blue color light, emotional arousal was estimated associated with skin sympathetic nerve inhibition. This study may suggest color lights affect mood, thermesthesia and thermoregulation through cognitive process.

低体温は,広い意味での呼吸(肺胞から末梢組織でのガス交換)・循環に大きな影響を及ぼすが,その影響は,低体温に陥った状況によりさまざまである。すなわち,救急外来に運ばれてきた低体温でも,事故や疾患の種類(寒冷環境への長期曝露や脳疾患,意識消失などに伴う体温調節反応の減弱など)によって異なるし,病院の中でも,病棟で起こったか,手術室で起こったかで大きく異なる。また近年,低体温療法が脳や心筋障害時の臓器保護の方法として用いられるようになり,低体温が人為的に行われる場合もある。病棟や手術室においても,補液や循環管理がなされているか,気道が確保されているか,さらには人工呼吸器でコントロールされているか,麻酔薬や筋弛緩薬,カテコールアミンが用いられているか,などによって呼吸・循環への影響は大きく異なる。もちろん,肺や呼吸中枢,心臓・血管にかかわる基礎疾患の有無にも左右される。本稿では,以上のような個別の状況に応じて低体温の影響を評価するために必要になる,基礎的な低体温時の呼吸・循環の変化について解説する。(著者抄録)

We examined the regional sensitivity in temperature sensation and thermal comfort/discomfort. Subjects sitting in a 33&amp;deg;C environment were locally cooled and warmed with water perfused stimulators (270cm&lt;SUP&gt;2&lt;/SUP&gt;). The water for basal, cooling, and warming conditions was set at 35&amp;deg;C, 25&amp;deg;C, and 42&amp;deg;C respectively. The areas stimulated were the neck, abdomen, hand and sole. Each stimulus lasted 90 s. Temperature sensation and thermal comfort/discomfort of stimulated area and those of whole body were reported by the subjects. At the basal condition just before the local stimulation of each area subjects reported hot and uncomfortable for whole body sensations. At the end of 90 s cooling, subjects reported clear cold sensation for local temperature sensation and no significant difference was observed among those of the four areas. But for local thermal comfort/discomfort at the same time point, depended on the area stimulated. While abdominal cooling produced no pleasant feeling, cooling of the other parts produced clear pleasant sensation. As for local warming, at the end of 90 s stimulation subjects reported hot and uncomfortable sensation and no significant difference was observed among those of the four areas. These results show that humans tend to keep the abdomen warm even during whole body heat exposure. &lt;b&gt;[J Physiol Sci. 2008;58 Suppl:S102]&lt;/b&gt;

We have shown that circadian body temperature (T&lt;SUB&gt;b&lt;/SUB&gt;) rhythm is finely regulated, but feeding condition affects largely the T&lt;SUB&gt;b&lt;/SUB&gt; rhythm. During fasting, T&lt;SUB&gt;b&lt;/SUB&gt; gradually decreases in the light (inactive) phase, whereas T&lt;SUB&gt;b&lt;/SUB&gt; in the dark (active) phase is maintained at the free-feeding level. The purpose of this study was to elucidate the mechanism involved in the altered thermoregulation between dark and light phase during fasting. Male ICR mice (2-3 mo old) were housed at an ambient temperature (T&lt;SUB&gt;a&lt;/SUB&gt;) of 27&amp;deg;C in a 12:12-h light-dark cycle. After 48-h fasting, cold exposure (T&lt;SUB&gt;a&lt;/SUB&gt;=20&amp;deg;C) was carried out at light phase (ZT1-4) or dark phase (ZT13-16). T&lt;SUB&gt;b&lt;/SUB&gt; (biotelemetry) and oxygen consumption (VO&lt;SUB&gt;2&lt;/SUB&gt;, indirect calorimetry) were measured. c-Fos immunostaining was also performed after the cold exposure. During the cold exposure with fasting, T&lt;SUB&gt;b&lt;/SUB&gt; decreased by 5.5 &amp;plusmn; 2.0&amp;deg;C at light phase, and VO&lt;SUB&gt;2&lt;/SUB&gt; remained unchanged. In contrast, at dark phase, T&lt;SUB&gt;b&lt;/SUB&gt; decreased by only 2.0 &amp;plusmn; 0.5&amp;deg;C with an increase in VO&lt;SUB&gt;2&lt;/SUB&gt; (p&lt;0.05), which was greater than that in the light phase (p&lt;0.05). The number of c-Fos-immunoreactive cells after the cold exposure with fasting were greater at the dark phase than the light phase in the medial preoptic area, dorsomedial hypothalamus, paraventricular hypothalamic nucleus, and arcuate nucleus. These results indicate that fasting attenuates thermoregulatory response to the cold, and the response differs among time of the day. The difference between the dark and light phase would be partially due to the neuronal activity in the hypothalamus. &lt;b&gt;[J Physiol Sci. 2008;58 Suppl:S87]&lt;/b&gt;

&lt;B&gt;INTRODUCTION&lt;/B&gt; We reported that, in ovariectomized rats, thermoregulation in the cold was attenuated. Systemic administration of 17-&amp;beta;estradiol (E&lt;SUB&gt;2&lt;/SUB&gt;) restored the attenuated response. E&lt;SUB&gt;2&lt;/SUB&gt; increased &lt;I&gt;cFOS&lt;/I&gt; immunoreactive cells in the medial preoptic area ( MPO ) and dorsomedial hypothalamus ( DMH ) in the cold. In the present study, we hypothesized that E&lt;SUB&gt;2&lt;/SUB&gt; would upregulate thermosensitivity to the cold at the level of the hypothalamus. To test this hypothesis, we assessed the effect of the local administration of E&lt;SUB&gt;2&lt;/SUB&gt; to the two hypothalamic areas on body temperature ( T&lt;SUB&gt;b&lt;/SUB&gt; ) in the cold. &lt;B&gt;METHODS&lt;/B&gt; Adult female rats were ovariectomized, and a stainless steel canula was placed in the MPO, DMH, or horizontal limb diagonal band. At least 7 days after the surgery, E&lt;SUB&gt;2&lt;/SUB&gt; or cholesterol was administrated to this brain area through the canula. Forty-eight hours after the administration, a rat was exposed to 10&amp;deg;C or 25&amp;deg;C environment for 2h, and T&lt;SUB&gt;b&lt;/SUB&gt; was continuously measured. &lt;B&gt;RESULTS&lt;/B&gt; During the 10&amp;deg;C exposure, T&lt;SUB&gt;b&lt;/SUB&gt; increased only in the group, which is administrated E&lt;SUB&gt;2&lt;/SUB&gt; in the MPO. Either cholesterol nor E&lt;SUB&gt;2&lt;/SUB&gt; in the other brain area had no effect on T&lt;SUB&gt;b&lt;/SUB&gt;. &lt;B&gt;CONCLUSION&lt;/B&gt; The MPO has abundant estrogen receptors and so-called thermosensitive neurons, estrogen may modulate thermosensitivity to the cold in the MPO. We also clarified the mechanism, based on &lt;I&gt;cFOS&lt;/I&gt; immunoreactivity in the hypothalamic areas and &lt;I&gt;UCP1&lt;/I&gt; mRNA expression in the interscapular brown adipose tissue. &lt;b&gt;[J Physiol Sci. 2008;58 Suppl:S100]&lt;/b&gt;

&lt;B&gt;Introduction&lt;/B&gt; We have reported that estrogen has influence on thermoregulation in the heat and cold. In ovariectomized rats, in the heat, an increase in body temperature (T&lt;SUB&gt;b&lt;/SUB&gt;) was greater with a reduction in heat dissipation from the skin. In the cold, T&lt;sub&gt;b&lt;/sub&gt; was smaller with a decrease in metabolic heat production. However, 17&amp;beta;-estradiol (E&lt;SUB&gt;2&lt;/SUB&gt;) replacement restores these responses to normal levels. The purpose of the present study was to test the hypothesis that the estrogen fluctuation in normal estrus cycle would modulate the thermoregulary response to the cold in rats. &lt;B&gt;Methods&lt;/B&gt; Female WKY rats were laparectomized and radiotelemeters for T&lt;sub&gt;b&lt;/sub&gt; were placed. At least 2 wks after the surgery, rats&#039; vaginal smear was obtained to determine the estrus cycle. At 9 am, rats in proestrus or diestrus period were exposed to 5&amp;deg;C or 25&amp;deg;C environment for 2 h, and T&lt;SUB&gt;b&lt;/SUB&gt; was monitored. After the cold exposure, rats were perfused with phosphate buffered saline and the brains were excised. cFos immunoreactive cells in the hypothalamic area were counted. &lt;B&gt;Results&lt;/B&gt; T&lt;SUB&gt;b&lt;/SUB&gt; increased in the cold in the proestrus period, but decreased in the diestrus period. Plasma E&lt;SUB&gt;2&lt;/SUB&gt; was higher in the proestrus period than estrus period with a small difference in progesterone level. cFos immunoreactive cells in the medial preoptic area and dorsomedial hypothalamus were greater in the proestrus period. &lt;B&gt;Conclusion&lt;/B&gt; Thermoregulation in the cold differs among the periods of estrus cycle in rats. The fluctuation of plasma E&lt;SUB&gt;2&lt;/SUB&gt; level may be involved in the mechanism. &lt;b&gt;[J Physiol Sci. 2008;58 Suppl:S60]&lt;/b&gt;

We examined the regional difference in temperature sensation and thermal comfort/discomfort. Subjects sitting in a 32-33&amp;deg;C environment were locally cooled and warmed with water perfused stimulators. The areas stimulated were the face, chest, abdmen and thigh. The temperature of water for cooling was 25&amp;deg;C, and that for warming was 42&amp;deg;C. The area of stimulation was 270 cm&lt;SUP&gt;2&lt;/SUP&gt; and each stimulation lasted 1.5 min. Temperature sensation and thermal comfort/discomfort of stimulated area and those of whole body were reported by the subjects using dials numbered from -10 to 10 (0 : neutral). The setting of the dial procedured a voltage which was continuously recorded. At the basal condition without local stimulation subjects reported hot and uncomfortable for whole body sensation. During local thermal stimulation there is no significant difference in local temperature sensation among the four areas. But for thermal comfort/discomfort, face and abdmen displayed characteristic sensation for cold stimulation. Thermal comfort was strongest for the face by cooling. On the other hand, abdominal cooling produced discomfort even in the hot environment. These results suggest that there is regional difference in the production of thermal comfort/discomfort. &lt;b&gt;[J Physiol Sci. 2007;57 Suppl:S184]&lt;/b&gt;

&lt;B&gt;Introduction&lt;/B&gt; Body temperature is finely regulated, although feeding condition is a factor modulating the regulation. Fasting is a strong stimulus reducing metabolism (i.e. heat production). However, body temperature is well maintained in the active phase, indicating change in thermoregulation. I discuss about neural and hormonal mechanisms involved in the change in thermal regulation during fasting and the possible role of clock genes. &lt;B&gt;Experiments and Results&lt;/B&gt; 1) Fasting induced greater reduction of metabolism and its circadian amplitude. Although the reduction of heat production, body temperature rhythm was well maintained except for greater decrease of body temperature around the lights onset. During the fasting, body surface temperature was greatly reduced, meaning that heat loss mechanisms were suppressed. 2) During fasting, heat producing response to the cold was attenuated in rats. However, this response is attenuated in the presence of i.c.v. leptin. 3) Feed-fast cycle generated daily oscillation of body temperature in clock mutant and cry knockout mice, both mice could not modulate heat loss responses to the fasting. 4) Fasting affects neural activities in the suprachiasmatic nucleus, estimated by c-Fos expression. &lt;B&gt;Conclusion&lt;/B&gt; Fasting is a strong signal modulating thermal regulation. Leptin level in the central may be a factor to change metabolic activity, deactivating the sympathetic nerves to the brown adipose tissue. Moreover, circadian clock receive fasting signals, which may alter heat loss responses and maintain body temperature rhythm. &lt;b&gt;[J Physiol Sci. 2007;57 Suppl:S32]&lt;/b&gt;

著者らは長時間水蒸気を発生する蒸気温熱(HSG)シートを作製した.これを水蒸気を発生しない乾熱(HG)シートと比較し,その体温調節反応および感覚に及ぼす効果について検討した.その結果, 1)シート適用部直下の皮膚温度はHSGシートとHGシートで同等であったにもかかわらず,シートから外側2cmの皮膚温度はHSGシートでおよそ0.9℃高かった. 2)被験者はHSGシートを適用したとき,HGシートに比べて体全体の冷え感覚が有意に抑制され,加温部の温感がより温かくより広範囲に広がる感覚が得られた. 3)熱流束測定装置を用いた別個の試験では,HSGシートとHGシートは同じ表面温度であったにもかかわらず,HSGシートの熱流束はHGシートの熱流束よりも高かった.以上,これらのことからも,蒸気で皮膚を加温することは乾いた熱で加温することに比べてより効果的であることが示唆された

We investigated the effects of alcohol on thermoregulatory responses and thermal sensations during cold exposure in humans. Eight healthy men participated in this study. Experiments were conducted twice for each subject at a room temperature of 18 &amp;deg;C. After a 30-min resting period, the subject drank either 15% alcohol (alcohol session) at a dose of 0.36 g/kg body weight or an equal volume of water (control session). Deep body temperature gradually decreased throughout 90-min measurement both in the alcohol and control sessions (from 36.9 &amp;plusmn; 0.1 &amp;deg;C to 36.6 &amp;plusmn; 0.1 &amp;deg;C) without any statistically significant differences. Metabolic rate in the control session started to increase 30 min after the onset of measurement. On the other hand, in the alcohol session, metabolic rate remained unchanged in spite of a decrease in body core temperature. Whole body cold sensation became strong in the control session during cold exposure, whereas it changed to &quot;not cold at all&quot; after alcohol drinking, which would inhibit the behavioral regulation, if available. In the previous study we have already shown that both autonomic and behavioral thermoregulation is also modulated to decrease body temperature in hot environment (Yoda et al., 2005). Thus, alcohol influences all thermoregulatory mechanisms including behavior so as to decrease body core temperature. These results suggest that alcohol affects some elements common to all the effector mechanisms, most presumably thermosensitive neurons in the brain. &lt;b&gt;[J Physiol Sci. 2006;56 Suppl:S229]&lt;/b&gt;

Heat loss responses are suppressed during dehydration, and hyperosmolality in the extracellular fluid is thought to be involved in this mechanism. In an &lt;I&gt;in-vitro&lt;/I&gt; brain slice, warm-sensitive neurons in the medial preoptic area (MPA) are deactivated in a hyperosmotic medium. In contrast, neural activities in the median preoptic nucleus (MnPO) increase during both heat and osmotic stimuli. In the present study, we hypothesized that tail vasodilatation induced by local warming of the MPA in urethane-anesthetized rats would be suppressed by a selective infusion of hypertonic saline to the brain. In addition, rats with the MnPO lesion would lack this suppression. The MPA warming at &amp;sim;40 &amp;deg;C increased skin temperature at the tail. Hypertonic saline (1500 mM) infusion into the left internal carotid artery suppressed this response when the MPA was warmed in its dorsolateral area. In MnPO-lesioned rats, there was no effect of hypertonic-saline infusion on the tail skin temperature during the MPA warming. These results indicate that the tail vasodilatation elicited by MPA warming is suppressed during osmotic stimulus. Moreover, the dorsolateral area in the MPA is a crucial site for such a response. The MnPO is also involved in this mechanism. &lt;b&gt;[J Physiol Sci. 2006;56 Suppl:S231]&lt;/b&gt;

Recent instruments for the study of thermoregulation in rodents are usually large and often require troublesome trainings of animals. In this study, we designed, made and tested a new simple instrument for investigating rodents&#039; behavioral thermoregulation. The apparatus was composed of two stainless-steel hollow plates (plate A and plate B) with a length of 20cm and width of 5cm. Each plate had an inlet and an outlet that were connected to a separate constant-temperature bath (bath 1 and bath 2). The water temperatures of the baths were controlled at one designated temperature within 10 and 45 degrees and pumped into the plates. A change switch for the water supply was inserted between both the plates and the baths. In the normal switch position, bath 1 supplied water plate A, and bath 2 supplied water plate 2, and in the reverse position, vice versa. Plates A and B were arranged and covered with a surrounding transparent fence 20cm high in a climatic chamber. A rodent stayed inside the fence and moved on plate A or plate B. The position of the rodent was observed by a video camera. We tested thermoregulatory behavior of eight male mice using this instrument. By shuffling the plate temperatures between 10 and 45 degree, the mice moved to the plates with a temperature close to the 35 degree. The findings implied our instrument might be useful as an apparatus for the study of behavioral thermoregulation. &lt;b&gt;[J Physiol Sci. 2006;56 Suppl:S227]&lt;/b&gt;

Body temperature (T&lt;sub&gt;b&lt;/sub&gt;) is different between male and female, e.g. daily change in T&lt;sub&gt;b&lt;/sub&gt; is fluctuated with menstruation cycle in female rats. We hypothesized that estrogen plays a crucial role in the sex difference in T&lt;sub&gt;b&lt;/sub&gt;. &lt;B&gt;Methods&lt;/B&gt; (1) Daily change of T&lt;sub&gt;b&lt;/sub&gt; was measured after gonadectomy in male and female rats. After the measurement, silicon tubes containing 17-beta estradiol (E&lt;sub&gt;2&lt;/sub&gt;) crystalline, aimed to maintain blood estrogen constant, were subcutaneously placed in the rats. Then T&lt;sub&gt;b&lt;/sub&gt; measurement was repeated. (2) Thermoregulation during 2-h heat exposure at 34&amp;degC or cold exposure at 5&amp;degC was assessed in gonadectomized female rats, and the same protocol was conducted in those with E&lt;sub&gt;2&lt;/sub&gt; tubes. &lt;B&gt;Results&lt;/B&gt; (1) Compared with male rats, T&lt;sub&gt;b&lt;/sub&gt; rhythm in female gonadectomized rats became unstable, showing 2-4 h irregular oscillations. T&lt;sub&gt;b&lt;/sub&gt; rhythm remained unchanged in male gonadectomized rats. In female gonadectomized rats with E&lt;sub&gt;2&lt;/sub&gt; tubes, T&lt;sub&gt;b&lt;/sub&gt; rhythm returned to the normal level. However, there was no influence of E&lt;sub&gt;2&lt;/sub&gt; on T&lt;sub&gt;b&lt;/sub&gt; rhythm in the male rats. (2) Both in the heat and cold, gonadectomized female rats could not maintain their T&lt;sub&gt;b&lt;/sub&gt; as those with E&lt;sub&gt;2&lt;/sub&gt; tubes. Histological analysis for the rat brain showed that Fos-immunoreactive cells in the hypothalamus were smaller in the rats without E&lt;sub&gt;2&lt;/sub&gt; tubes. &lt;B&gt;Conclusion&lt;/B&gt; These results show that estrogen is involved in the thermoregulation in female rats. Estrogen may modulate thermal sensitivity to the environment at the level of the hypothalamus &lt;b&gt;[J Physiol Sci. 2006;56 Suppl:S102]&lt;/b&gt;

Oxidative DNA damage produced by reactive oxygen species (ROS) has been considered as a cause of degenerative processes associated with aging. Generation and reactivity of ROS, which involve chain chemical reactions, depends on body temperature. Thus, ROS would be produced more with increase in body temperature. However, it has yet to be clarified how a change in body temperature modifies the oxidative DNA damage in human. To investigate the effects of rectal temperature after bath on oxidative DNA damage in human, by measuring its biomarker, urinary 8-hydroxydeoxyguanosine (8-OHdG). We determined the urinary 8-OHdG levels of two healthy male volunteers and immersed men at two different water temperatures for 10min. They immersed both in a water bath of 39℃and 42℃ for 10 min, after which exposes 25℃ in the environment for 120 min. The urine 8-OHdG was used at selected time points: pre-, just post-experiment, 2 hr post-experiment, 6 hr post-experiment, 12 hr post-experiment and 24 hr post-experiment. The level of urinary 8-OHdG excretion change significantly compared to each control, at 39℃ did it increase from 2 hr post-experiment, at 42℃ did it increase from just after the bath. The daily average of urinary 8-OHdG excretion, there was a difference in urinary 8-OHdG excretion between 39℃ and the control 42℃ (263±55. 7pmol/kg/day 39℃ vs 454±99. 8pmol/kg/day 42C) . These results suggest that different water temperature produces oxidative DNA damage that might promote body tissue injury.

It is well known that thermoregulation is different between male and female, although the mechanism remains unclear yet. The purpose of this study is to investigate the role of estrogen on thermoregulatory mechanisms for daily change of body temperature (T&lt;SUB&gt;b&lt;/SUB&gt;). Fist, we measured daily changes in Tb, metabolism, and body surface temperature in gonadectomized male and female rats (n=6 each) under 12:12h light-dark condition. Compared with normal rats, T&lt;SUB&gt;b&lt;/SUB&gt; in the female gonadectomized rats became unstable, showing 2-4 h irregular small oscillation, although chi-square analysis indicated that the period of the rhythm remained 24 h. However, there was no change in the T&lt;SUB&gt;b&lt;/SUB&gt; rhythm in the male gonadectomized rats. Second, silicon tubes containing E2 crystalline were subcutaneously implanted in the gonadectomized rats. In the female gonadectomized rats with the tubes, the T&lt;SUB&gt;b&lt;/SUB&gt; rhythm was restored to the normal pattern. However, there was no influence of E2 on the T&lt;SUB&gt;b&lt;/SUB&gt; rhythm in the male rats. The T&lt;SUB&gt;b&lt;/SUB&gt; change due to the gonadectomy is closely linked with both metabolism and body surface temperature. These results indicate that E2 is involved in the thermoregulation for daily change of T&lt;SUB&gt;b&lt;/SUB&gt; in female rats, but not in male rats. We also hypothesized that central neurons reacting both thermal and E2 stimuli would be closely associated with the mechanism. Therefore, histological analysis was conducted to test the hypothesis. &lt;b&gt;[Jpn J Physiol 55 Suppl:S220 (2005)]&lt;/b&gt;

The sensation related to temperature is complex in that there are two different kinds of sensation, subjective &amp;ldquo;thermal comfort&amp;rdquo; and objective &amp;ldquo;temperature sensation&amp;rdquo;, and in that we feel local as well as whole body sensations. And it is not clear how these different sensations are related with each other. To investigate this question we developed a new system to measure the distribution of whole body skin temperature and the two sensations in human. Skin temperatures (Tsk) of in total 50 points on both sides of the body were measured by thermocouples, and local heat flux was also measured at 25 points by heat flux sensors. Core temperature (Tcore) was measured by telemetric system (CoreTemp), the transmitter of which was swallowed by a subject. Temperature sensation (cold-neutral-hot) and thermal comfort (uncomfortable-neutral-comfortable) of 25 points of body surface, and those of the whole body were reported by the subject using a console with 52 dials for each sensation. Color-coded Tsk and sensations were displayed on the computer display. This system enables to see the distribution and change of Tsk and sensations over the body surface even with clothes on, and should be useful for the analysis of temperature-related sensations as well as the design of comfortable environment or clothes. &lt;b&gt;[Jpn J Physiol 55 Suppl:S221 (2005)]&lt;/b&gt;

Various homeostatic systems are under the control of the circadian clock. Recently we found that fasted rats kept under a light-dark cycle showed a decrease in body temperature (Tcore) only during the light phase. In the fasting condition, in the dark phase Tcore was maintained normal by a suppression of heat loss mechanism despite the reduction of metabolic heat production. In contrast, the response was weakened in the light phase, decreasing Tcore greatly, but in this period cold escape behavior is facilitated, probably for the compensation of Tcore decrease. These modulations of thermoregulatory effectors, depending on the time of the day, are considered as adaptive responses to the lack of food. Interestingly, in the rats with the lesion of the hypothalamic suprachiasmatic nucleus in which daily rhythms of Tcore and activity were abolished, body temperature was unchanged by food deprivation. Very similar loss of Tcore modulation was observed in those mice lacking the criptochrome genes (Cry1&lt;sup&gt;&amp;minus;/-&lt;/SUP&gt;/Cry2&lt;sup&gt;&amp;minus;/-&lt;/SUP&gt;) during food restriction. These results suggest that the circadian clock is a key structure for coordinating the controls of body temperature, energy metabolism, and behavior. &lt;b&gt;[Jpn J Physiol 54 Suppl:S7 (2004)]&lt;/b&gt;

Kei Nagashima, Dept Physiol, Waseda Univ Sch Human Sci&lt;Br&gt;&lt;B&gt;A reduction in body temperature during fasting in rats&lt;/B&gt;&lt;Br&gt;Body temperature (T&lt;sub&gt;b&lt;/sub&gt;) is determined by the balance between heat production and heat loss. In rats, T&lt;sub&gt;b&lt;/sub&gt; is linked with heat production during free-feeding. Fasting reduces the production of heat throughout a day; however, T&lt;sub&gt;b&lt;/sub&gt; is maintained during the dark phase and decreases markedly during the early light phase. The reduction in T&lt;sub&gt;b&lt;/sub&gt; would protect animals from excessive heat loss, minimizing the temperature difference between the body and environment. Temperature of the tail, reflecting active heat loss, also decreases during the fasting. These results indicate that rats suppress heat loss to maintain T&lt;sub&gt;b&lt;/sub&gt;. However, the suppression is weaker in the light phase than dark phase, which would be a mechanism involved in the reduction in T&lt;sub&gt;b&lt;/sub&gt;. Although it still remains unclear if rats control the phase-specific change in thermoregulation, a couple of evidences proving the possibility are presented in this symposium. When the suprachiasmatic nucleus (SCN, the master clock for circadian rhythm) are lesioned, the reduction in T&lt;sub&gt;b&lt;/sub&gt; does not occur, although metabolic heat production decreases in the same manner as the sham-operated rats. Moreover, when rats are exposed to constant darkness, the reduction is attenuated and the phase of the reduction is delayed. These results suggest that the reduction of T&lt;sub&gt;b&lt;/sub&gt; occurs in response to the stimulus originating the SCN. Moreover, the light is an important factor for this response. In summary, the reduction of T&lt;sub&gt;b&lt;/sub&gt; during low energy storage would be a regulated phenomenon linked with biological rhythm. &lt;b&gt;[Jpn J Physiol 54 Suppl:S56 (2004)]&lt;/b&gt;

We previously reported that s.c. hypertonic-saline increased operant heat-escape/warm-seeking behavior in rats. In this study, to assess the mechanism involved, the behavior was measured in rats of which the median preoptic nucleus (MnPO) was chemically ablated (ibotenic acid, 5 &amp;mu;g). The lesion was verified success by an attenuation of the drink after i.c.v. injection of angiotensin II. Thirty minutes after s.c. injection of either 2500- or 154-mM saline (1.0 ml/100 g), rats were successively placed at 26, 35 and 40&amp;deg;C for 1 h each. They could trigger 0&amp;deg;C-air for 45s when entered a specific area (i.e. operant behavior). In the sham-operated rats, counts of the operant behavior was greater (&lt;I&gt;p&lt;/I&gt;&lt;0.05) in 2500-mM than 154-mM saline during 35 and 40&amp;deg;C-heat. However, in the lesioned-rats, the counts did not differ between the two trials, and were at the same level as those in the sham-operated rats in 154-mM saline trial. These results suggest that the MnPO is involved in the mechanism which activates heat-escape/warm-seeking behavior after hypertonic-saline injection. Howeover, the MnPO is not associated with the behavior in euhydrated condition. &lt;b&gt;[Jpn J Physiol 54 Suppl:S230 (2004)]&lt;/b&gt;

1)造血能亢進程度に年齢ならびに体重による有意差は認めなかった. 2)rHuEPO投与及び貯血による重篤な合併症は認めなかった

予定開心術症例12例に対し,rHuEPO;200U/kgを術前14日目鉄剤と共に静脈内に連日投与した結果,全例でHb濃度が増加したが,症例によりその増加の程度に差を認めた.この原因を探るべく,術前状態及び術前諸検査値とHb増加濃度との相関関係を検討したが,決定的な関係を見いだすことはできずこれらからrHuEPO投与によるHbの増加の程度を投与前に推定することは困難と思われた.また,網赤血球産生指数及び骨髄像からみて明らかに造血能は亢進しているにも関わらずHb濃度の増加にかならずしも反映されず,以前から言われているもの以外にも造血能亢進を妨げる何らかの因子が存在している可能性が示唆された

38歳女,胸部X線異常陰影と同時期より続く乾性咳を主訴とした。上前縦隔良性腫瘍の診断の下に胸骨縦切開にて摘出手術を行った。腫瘍は反回神経分岐より中枢の左迷走神経本幹より発生していた。腫瘍に接した神経束の腹側を長軸方向に部分切除し,迷走神経を切離せずに被膜を含め腫瘍を摘出した。術後嗄声等の合併症は認めず,組織診断で神経鞘腫であった

膵腺房細胞癌はまれな腫瘍であるが,機能性腫瘍として外分泌作用を生じることもあるといわれている.予後に関しては悲観的な報告が多い.当院で,多発早期胃癌に併存し肝転移をきたしていた微小膵腺房細胞癌に対し胃全摘,膵尾部切除,肝切除を行い術後1年再発なく経過した症例を経験したので報告する.

The goal of present study was to clarify the mechanism involved in generation of circadian body temperature rhythm. In the research, we hypothesized that 1) the suprachiasmatic nucleus (SCN), i. e. the central for circadian rhythms modulates thermosensitiveity at the levels of the central and periphery, and 2) the body temperature rhythm is important in synchronizing the rhythms of the central and periphery. In experiments, mice were exposed to the cold at 20℃ after ad-lib feeding or 48-h fasting, then we estimated metabolic heat production and UCP1 mRNA in the brown adipose tissue. In addition, cFos expression reflected by neural activity in the hypothalamus was also estimated. The same experimental protocol was repeated on Clock mutant mice, which lacks normal circadian rhythmicity. During ad-lib feeding, there were no differences in thermoregulatory responses and cFos expression in the cold. However, during fasting, heat production response was apparent only in the dark phase, and cFos expression in the SCN was augmented in the light phase. There were no phase-differences in the responses in Clock mutant mice. We also found an inhibitory network from the SCN and paraventricular nucleus associated with the sympathetic nerve activity. The SCN was influenced by environmental temperature and feeding condition, which is involved in time-dependency of body temperature regulation.

目的 女性ホルモンはホットフラッシュ、冷えなどの女性特有な体温調節、感覚異常に関係していると考えられている。しかしながら、その明確なメカニズムは明らかではない。本年度は、女性ホルモンがi)体温概日リズムにいかに影響を与えるか,ii)暑熱、寒冷暴露時の体温調節反応にいかに影響を与えるか iii)性周期に応じて体温調節反応、温度感覚はいかに変化するかを調べるとともに、そのメカニズムを検討した。i,iiについては動物実験にて検証し、血については人での実験を行った。方法と結果 i)卵巣摘出ラットを用いて1週間の体温の変更を無拘束に記録した。約24時間の周期性は認めたが、3-4時間周期の大きな体温変動成分が現れるリズム変調が生じた。この変調は皮下に17beta-estradiol含有シリコンチューブを埋め込むことにより改善した。ii)卵巣摘出ラット、および17イ-estradiol含有シリコンチューブ皮下埋め込みによるエストロゲン補充を行ったラットの33℃,5℃の環境温での耐暑、耐寒反応を比較した。耐暑、耐寒反応とも卵巣摘出ラットでは低下しており体温が各々エストロゲン補充ラットに比べて、上昇もしくは低下した。このメカニズムを明らかにするために、視床下部でのcFOS発現を調べた。暑熱下では内側視索前野、寒冷下では背内側核に多くの発現画あったが、体温の変動は少ないのにも関わらず、エストロゲン補充ラットで多くのcFOS発現が認められた。iii)28℃の温度中性域から、23℃の中度寒冷環境下に若年女性を、黄体期、卵胞期に各々暴露した。深部温は、28℃,23℃とも黄体期に高かったが、温度感覚は同一であった。結語 女性ホルモンは,体温調節に大きな影響を与える。また、このメカニズムとして、中心温に対する脳での温度感受性のエストロゲンの変化であると予想した。

The preoptic area(POA) in the hypothalamus occupies a crucial position in the neuronal circuit for thermoregulation. Recently, the dorsomedial hypothalamus(DMH) was reported to be involved in the control of heat production. Therefore, in the present study, we investigated the brain areas that had functional afferent connections with the dorsomedial hypothalamus(DMH) for thermoregulation in rats, using immuno-histochemical analyses of a retrograde tracer, cholera toxin-b(CTb), injected into the DMH and Fos expression in response to warm (33℃) or cold (10℃) exposure. A double-labeled cell was defined as the neuron had functional connection with the DMH in relation to thermoregulation. In the warm-exposed rats, double-labeled cells were obtained only in the median preoptic area(MnPO). In the cold exposed rats, double-labeled cells were obtained in the anterior hypothalamus(AH), especially in its medial and ventral parts. The results in the Fos and CTb studies raised a possibility that the DMH neurons would be inhibited by the MnPO neurons, and CTb-IR neurons in the MnPO would be GABAergic and directly regulate activity of the DMH neurons. To examine this possibility, we further investigated an expression of mRNA for GAD67,a marker for GABAergic neuron, in CTB-IR MnPO neuron. We found that 79.6% of CTb-IR cells in the MnPO exhibited signals for GAD67 mRNA. These results suggest that the neurons in the POA, especially in the MnPO, receive warm inputs from the skin and send inhibitory signals, via GABAergic synapses, to the DMH to suppress heat production, and the neurons in the AH receive cold signals from the skin and send excitatory signals to the DMH, to activate heat production.

It is well known that body temperature (T_b) follows a circadian rhythm. Despite recent advance in knowledge of thermoregulation, we know only a little about the mechanism of the T_b rhythm. In this symposium, we show several evidences proving that i) the prime mechanism for the circadian T_b rhythm is a change in characteristics of thermoregulatory processes according to circadian phases, ii) clock genes and the suprachiasmatic nucleus are involved in the mechanism.
T_b rhythm during fasting. In ad-lib feeding rats, T_b rhythm was linked with heat production rhythm. Moreover, tail surface temperature reflecting active heat loss also changed linearly with the T_b rhythm. Thus it is thought that heat production dominantly determines the T_b rhythm in fed condition. Although heat production decreased and its circadian amplitude was blunted during 3-day fasting, the T_b rhythm was well maintained. Moreover, the tail temperature decreased greatly in the active phase. These results suggest that animals control their circadian T_b rhythm by modulating thermoregulatory responses, which depends on feeding and/or nutritional states.

「冷え性」は一般に良く使われているが、その病態はほとんど研究されていない.これまで行われているのは主として漢方医学の方面からのアプローチで、そこでは「末梢血管運動障害」と捉えられることが多い.本研究では冷え性の病態を生理学的に明らかにすることを目的に実験を行った。あらかじめインタビューから冷え症と考えている女性を中程度の寒冷(23℃)に曝露すると、冷え症ではない女性に比べて同じ深部温、皮膚温の条件でもより強く「寒さ」を申告した.また冷え症の女性は甲状腺ホルモン(T4)が正常範囲ではあるが非冷え症群に比べて低く、代謝量も低い傾向にあった.つまり「冷え症」の女性は正常範囲とはいえ、甲状腺機能が低下している.その結果代謝量(熱産生量)が低くなる.すると体温を維持するために2つの反応が起こる.(1)熱放散を抑えるために皮膚血管が収縮する.これは特に動静脈吻合の発達した四肢末端部(手足)から起こる.皮膚血管の収縮は皮膚温の低下を招き、その結果末梢部で「冷え」を感ずるようになる.(2)一方、自律系による体温の調節不全(代謝量低下)は代償的に体温調節行動(寒冷逃避行動)を促進する.それは寒冷への感覚の感度亢進という形で現れるであろう.以上のように冷え性は代謝の低下に対する適応反応と考えられる。一人で生活する場であれば、温度環境をその人にとって快適に設定することは可能である.しかし多人数が同じ空間を共有する公共の場では温度環境は平均的な人たちにとっての快適なものに設定されがちである.すると少数グループになるであろう「低代謝」の人たちは冷え症を訴える結果になる.公共の場の環境設定にも個人差を考慮することが必要である。

The preoptic area (PO) plays a key role in body temperature regulation by integrating information about local brain temperature and other body temperatures, and by sending efferent signals to various effector organs. Our previous studies elucidated that thermoregulatory skin vasodilation is elicited by the activation of warm-sensitive neurons in the PO, while shivering and non-shivering thermogenesis are controlled by the inhibitory actions of warm-sensitive neurons. In the midbrain skin vasodilative neurons were located in the the ventrolateral portion of the rostral periaqueductal grey (rPAG), and neurons having excitatory effect on non-shivering thermogenetive are located in the ventrolateral part of the caudal PAG (cPAG). However, the direct connections between the PO or the rest of the hypothalamus and the PAG in terms of thermoregulation has not been fully documented. In the present study we investigated in the rat's brain the distribution of neurons that are activated by exposure to neutral (26 ゜C), warm (33 ゜C) or cold (10 ゜C) ambient temperature, and that also project to the rPAG or cPAG, by the immunohistochemical analysis of Fos and a retrograde tracer, cholera toxin- b (CTb). When the tracer injection was centered in the rPAG, many double-labeled cells were observed in the dorsal part of the median preoptic nucleus (MnPO) in warm-exposed rats but few double-labeled cells were observed in the MnPO in cold-exposed rats. On the other hand, when the tracer injection was centered in the cPAG, many double-labeled cells were seen in the the posterior hypothalamic area (PH) in the cold-exposed rats but few double- labeled cells were seen in the warm-exposed rats. These results suggest that the rPAG receives warm signals from the MnPO and the cPAG receives cold signals from the PH region, probably participating in the efferent pathway for thermoregulatory skin vasomotion and non-shivering thermogenesis, respectively.

[Background] It is well known that exercise training is a potent stimulus to increase blood volume (BV), which is determined by many factors, i.e. renal water and Na^+ handling and fluid movement between the cellular and extracellular spaces. However, it remains unknown which factor is involved in the mechanism for the increase in BV due to exercise training.
[Purpose] 1. Treadmill exercise can increase BV in rats -rats could be model animal to investigate the mechanism for BV increase-?
2. Albumin, major substance maintaining plasma oncotic pressure, could be a factor increasing BV?
[Methods] Rats were divided into two groups : exercise training and no training groups (Ex and Con, respectively, n=10 each). The Con group was housed in normal cages at 23℃ in LD 12:12 h. The Ex group was also housed in the same condition but had 1-h treadmill exercise for 4 weeks (5 days/week). The treadmill speed was set at 10 m/sec and the slope was increased from 0°to 15°every week. At the end of 3rd week, two catheter were placed in the right femoral and jugular veins, respectively. In 5th week plasma volume (PV) of each rat was determined by Evans Blue dye dilution technique. Hematocrit, plasma albumin and total protein and oncotic pressure were also measured, and BV and plasma albumin content were calculated. Albumin synthesis was evaluated by measuring albumin mRNA level in the liver using Nothem blotting technique.
[Results] BV and plasma volume in the Ex group was greater (P<0.05) than in the Con group (6.4 ± 0.2 and 4.8 ± 0.5 ml/100g body weight, respectively). Plasma albumin content was also greater (P<0.05) than in the Con group (0.13 ± 0.01 and 0.10 ± 0.01 ml/100g body weight, respectively). The expression of albumin mRNA in the liver was similar in the two groups.
[Conclusion] Four-week treadmill exercise could increase BV in rats. The increase in plasma albumin could be a mechanism for this response. Although the expression of albumin mRNA in the liver remained unchanged between the Ex and Con groups, exercise training may have facilitated albumin synthesis in the earlier period.

In the present study we developed systems for analyzing (1) thermal comfort sensation in human and (2) behavioral thermoregulation in rats. In humans we used fMRI to search the brain regions activated by whole body cooling or warming. For thermal stimulation we have developed a special bag in which a human subject laid in supine position. Temperature controlled air flow through the bag. Eight male subjects were exposed to cool air of 8 or 13℃ for 22 min and scored their thermal comfort in every 1 min. The subjective thermal comfort score was correlated with rCBF changes in bilateral amygdala ; i.e.the neural activity there increased as the subjects felt it cold. It is suggested that the amygdala plays some role in the genesis of thermal comfort and this system is considered to be useful to analyze thermal comfort sensation in human. The operant system used for the rat behavioral thermoregulation contains a box that can be convectively heated or cooled. A rat moves freely in the box. Its location is monitored photoelectrically while its deep body temperature is monitored by a telemetry system. In heat-escape experiments hot air (40℃) flows through the box. When the rat enters a reward zone the air source is switched and cold air (0℃) flows through the box for a given period (30 sec). Conversely, in cold-escape experiments cold air flows through the box and when the rat enters the reward zone the air source is switched to a warm one. Experiments show that rats quickly learn to stay near the reward zone and move in and out of it periodically. This system is based on behavior more natural than the frequently used lever-pressing response, and has many advantages for use in studies involving behavioral thermoregulation.

Thermosensitive neurons in the hypothalamus, especially in the preoptic area (PO), play important roles in thermoregulation (Boulant, 1980; Simon et al., 1986), but many hypotheses about signal processing in the hypothalamus have remained untested because we don't have precise enough information about the neuronal "network" there. Although it had long been almost an article of faith that warm-sensitive neurons send efferent signals driving heat loss and cold-sensitive neurons send efferent signals driving heat production, we found that warm-sensitive neurons work for the control of heat production as well as heat loss (Zhang et al., 1995). But we have obtained evidence that the PO is simply an assembly of neuronal groups, each sending its own efferent signals to each effector, and that these groups function without connections to each other (Kanosue et al., 1997). In the present study, based upon these findings, we further analyzed the neural network for thermoregulation in the hypothalamus and the midbrain. First, we analyzed the nertwork for nonshivering thermogenesis. Electrical stimulation of the ventromedial hypothalamus elicited thermogenesis of the brown adipose tissure. But the same stimulus had no effect during warming the preoptic area, which means that the PO send inhibitory signals to the VMH. Second, the role of the posterior hypothalmus was investigated by injecting inhibitory substance muscimol. Muscimol injection suppressed cold-induced shivering, which indicates that the excitatory neuron for shivering locates in the posterior hypothalamus. Third, DLH was injected into the ventropoterior region of the PAG and it facilitated nonshivering thermogenesis. The retrograde tracer CTB injection into the medullary raphe labeled neurons in the PAG where nonshivering thermogenesis was facilitated. The excitatory signal seems to decsend from the PAG to the raphe.

我々は絶食によって寒冷時の体温調節反応が弱められることを報告している（Tokizawa et al. Neuroscience 2009）。その反応は、マウスにおいて暗期と比べて明期（非活動期）に特に大きく弱められる。この時間特異性のメカニズムとして、時計遺伝子Clockおよび視交叉上核の神経活動亢進に伴う室傍核の活動抑制が関与することを我々は明らかにしている。しかし、絶食によって引き起こされるどのような因子が体温調節反応を減弱させるのか、また時間特異的な反応を引き起こすのかは明らかではない。そこで本研究では、絶食によって変化する摂食ペプチド（レプチンの低下、グレリンの増加）が時間特異的な体温調節反応に関与しているか否かを検証することを目的として行った。【２０１０年度　進捗状況報告】実験1：野生型およびレプチンを欠損するob/obマウスを、27℃の環境温で12h-12hの明暗サイクル（午前7時（ZT0）点灯，午後7時（ZT12）消灯）で飼育した。体温および活動量の概日リズムが確認された後、20℃の寒冷暴露を明期（ZT1～4）または暗期（ZT13～16）に行った。実験2：野生型マウスにおいて、腹腔内にグレリン（8 nmol）をZT1またはZT13に投与し、10℃の寒冷暴露を明期（ZT2～4）または暗期（ZT14～16）に行った。対照として、生理食塩水を投与する試行も行った。両実験において、寒冷暴露時の深部体温と活動量をテレメトリー、酸素摂取量を間接的カロリメトリーにてそれぞれ測定した。また寒冷暴露直後に脳を採取し、神経活動のマーカーであるc-Fos蛋白の免疫組織化学染色を行った。【結果】実験1：野生型マウスにおいては明期と暗期ともに、寒冷暴露によって深部体温は変化しなかった。また酸素摂取量は有意に増加した。ob/obマウスにおいて、寒冷暴露により深部体温は有意に低下した。明期と暗期の間で有意な差は認められなかった（明期、3.8 ± 0.8℃；暗期2.1 ± 0.3℃）。寒冷暴露によって酸素摂取量は増加したものの、野生型と比較して有意に低かった。c-Fos蛋白の免疫陽性細胞数は、視床下部のいずれの神経核においても野生型とob/obマウスの間で有意な差は認められなかった。実験2：グレリンを投与した野生型マウスにおいて、明期の寒冷暴露によって深部体温は生理食塩水投与と比較して有意に低下した。また酸素摂取量は増加したものの、生理食塩水投与と比較して有意に低かった。一方暗期においては、グレリン投与試行の寒冷暴露によって深部体温は低下せず酸素摂取量は有意に増加し、生理食塩水投与との間に有意な差は認められなかった。c-Fos蛋白の免疫陽性細胞数は、視交叉上核において明期にグレリン投与によって有意に増加した。また弓状核においては、明期と暗期ともにグレリン投与によってc-Fos蛋白の免疫陽性細胞数は増加したものの、暗期の方で増加は大きかった。室傍核において、グレリン投与のみではc-Fos発現は見られなかったものの、グレリン投与で寒冷暴露を行った暗期においては、c-Fos蛋白の免疫陽性細胞数は有意に増加した。【結論】レプチンの欠損は体温調節反応を弱めるが、絶食時に見られる時間特異的な体温調節反応の減弱には関与しないことが示唆された。一方グレリンの増加は、時間特異的に明期にのみ体温調節反応を弱める可能性が示唆され、絶食時に見られる時間特異的な体温調節に関与する可能性が考えられた。

【目的】本研究は１）絶食が体温調節反応に及ぼす影響を暗期（活動期）と明期（非活動期）に分けて解析し，体温調節にかかわる脳視床下部での神経核、生物リズムの形成にかかわっていると考えられている時計遺伝子の一つであるClockとの関与を明らかにすること、２）低体温を引き起こすシグナルとしてグレリンの関与を調べた．【方法】実験１：マウスの体温と活動量を連続測定し，2日間の絶食を行った．絶食開始時刻は午前9時もしくは午後9時とし，各々この時間の47時間後，午前8時（明期）と午後8時（暗期）に，20&#186;Cの寒冷暴露を行った．脳のcFosタンパクの免疫組織化学染色を行った．時計遺伝子Clockの変異マウスを用いて，同様の実験を行った．実験２：野生型マウスにグレリン（8 nmol）または生食を午前8時（明期）と午後8時（暗期）投与し、10℃の寒冷暴露を行った．【結果】実験１：絶食明期寒冷暴露時には，体温は30分目以降低下したが酸素摂取量に変化はなかった．絶食暗期寒冷暴露時には，130分目以降低下し，酸素摂取量は増加した．体温の低下は明期に暗期と比較して大きく，酸素摂取量の増加は暗期が明期に大きかった．視床下部のcFos免疫陽性細胞数は，内側視索前野および室傍核で暗期寒冷暴露に増加した．視交叉上核では，絶食、寒冷暴露によりcFosは増加した．Clock変異マウスでは，明期と暗期の間に差はみられなかった．実験２：グレリンを投与したマウスにおいて、明期の寒冷暴露により体温は低下した．酸素摂取量は低かった．暗期では、グレリン投与後の寒冷暴露により体温は低下せず酸素摂取量は増加した．cFos-は視交叉上核において明期にグレリン投与により増加した．【考察】１．摂食条件は体温調節に大きく関わっており，絶食時には寒冷時の体温調節反応を時間特異的に抑制することが明らかになった．時間特異的に抑制するメカニズムに時計遺伝子Clockが関与していることが明らかになった． 2.絶食時の低体温は調節された現象と考えられるが、絶食に伴い増加するグレリンは絶食時の時間特異的な体温調節に関与していると考えられる。

[目的]運動に伴う脱水は、発汗&#8226;皮膚血管拡張などの自律性体温調節反応の抑制を引き起こし、体温調節能の低下とともに、熱中症などにつながる。自律性体温調節とともに人では衣服の着脱、エアコンのオン&#8226;オフなどの行動性体温調節があり、自律性体温調節に対して相補的に働くと言われている。しかしながら、脱水時に行動性体温調節がいかに変化するかは未知のままである。今回の研究では、脱水時の行動性体温調節がいかに変化するのかを、人の行動性体温調節の動機である温度感覚&#8226;温熱的快不快感を指標に調べた。[方法]健康成人男子（22-28 y.o.）を対象にした。実験は２つの試行を１週間以上の間隔をおいて行った。１つめの試行は24°Cの環境下に~10%HRmaxの運動を、２つめの試行は35°Cの環境下に40%HRmaxの運動を各々40分間行った。その後27°Cから22°Cの環境まで、次に27°Cから38°Cの環境まで変化させこの間、深部体温、表面皮膚温、発汗率、皮膚血流、温度感覚、温熱的快不快感を測定し、運動前後&#8226;実験終了後の血液を採取した。[結果] 35°Cの環境下での運動では約1%体重の脱水が生じ、その後38°Cの環境で発汗、皮膚血流量の抑制が、24°Cの環境下での運動後の値に比較して見られ、深部体温も上昇した。しかしながら、温度感覚／温熱的快不快感については両者に差は見られなかった。[結論]暑熱下運動による軽度の脱水後にも、暑熱環境に暴露させると発汗、皮膚血流などの自律性体温調節反応が低下し、深部体温の上昇が見られた。しかしながら、温度感覚／温熱的快不快感には差が認められず、人においては自律性体温調節に対して行動性体温調節の動機となると予想される温度感覚／温熱的快不快感が相補的に亢進する証拠は認められなかった。

緒言　恒温動物には体温を一定に保つための優れたシステムが存在するが一方体温には明確な概日リズムが存在することが知られている。これは身体活動や代謝の活動により二次的に生じたものではなく積極的に調節されるものであることが申請者らの研究により明らかになってきている。目的　研究では生物時計の最上位中枢と考えられている脳視床下部の視交差上核がいかに体温調節反応を変化させ体温のリズムを形成しているかを明らかにしていくことを目的とした。実験１　ラットの視交叉上核を電気的に破壊し、十分な回復の後、高温（３３度）、低温（１８度）に暴露させこの際の体温調節を調べた。次に体内の熱産生を低下させる強い刺激である絶食をおこなった上で同様に体温の変動を測定した。結果　視交叉上核の破壊により体温のリズムは消失するが、いずれの環境温、摂食状態においても体温は一定に保たれた。しかし非破壊ラットにおいては絶食時に体温の低下が非活動期において認められた。さらに非破壊ラットにおいては環境温度の変動に対し熱産生量を変動させ体温を調節させるのに対し、視交叉上核破壊ラットではそのような反応が減弱していた。また摂食情報の伝達には迷走神経が重要な役割を果たしていることが付随する研究で明らかになった。実験２　時計遺伝子Cryの欠損マウスを用いてその体温の変動と熱産生の変動の関係を調べた。結果　Cryの欠損マウスでは体温の変動は熱産生の変動に依存している。一方正常マウスでは熱産生の変動に対しても体温を一定に保つメカニズムが存在した。結論　視交叉上核またその活動に反映する時計遺伝子は体温調節反応の制御に関わっていると考えられた。また摂食あるいは代謝の情報を視交叉上核はうけているとかんがえられ、さらに体温調節に影響をあたえていると推測される。上記研究結果についてはAmerican Journal of Physiology、Autonomic Neuroscienceに現在投稿中である。

テーマ「知ってびっくり！体温のヒミツ」

防寒の科学

カラダと水の微妙な関係

2012 熱中症対策マニュアル
猛暑到来！正しい知識で命を守れ！

2012 熱中症対策マニュアル
猛暑到来！正しい知識で命を守れ！夜間編

熱中症の発生の仕組についての解説

熱中症予防としての塩分摂取の是非、適応についてのコメント

座りっぱなし症候群解説

恒常性の維持についてのコメント

尿のトラブルについてのコメント

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

座りっぱなし症候群についての解説

頻尿＆残尿の原因＆対策は？

環境温度の感覚についての解説

環境温度の感覚についての解説