Thermoregulatory Set Point Research Articles

The influence of temporary semi-supine and supine postures on temperature regulation in humans

The present study was conducted to explore the influence of slight postural differences on temperature regulation in humans. The subjects were exposed to a hot environment for 50 min in two different postures (semi-supine and supine). Core body temperature fell consistently in spite of the very high atmosphere temperature in both postural conditions. Tympanic temperature became significantly lower in supine than in semi-supine posture in contrast with the parallel drops of esophageal and rectal temperature. Our results suggest that the temporary horizontal supine position (1) lowers the thermoregulatory set-point, and (2) enhances selective brain cooling in hyperthermia.

The administration of exogenous melatonin during the daytime lowers the thermoregulatory setpoint in humans

(1) The present study was conducted to explore the influence of melatonin administration during the daytime on both tympanic temperature ( T ty) level and the T ty threshold for autonomic thermoregulation. (2) Melatonin administration at 11:00 h (3-mg oral dose) caused a rapid T ty reduction. (3) After melatonin administration, cutaneous vasodilation and local sweating of the forearm occurred at significantly lower T ty than after the placebo during the local body warming with hot water bath at 42°C. (4) Our results show that the melation administration during the daytime lowers the thermoregulatory setpoint in humans.

Hypoxic metabolic response of the golden-mantled ground squirrel.

We examined the magnitude of the hypoxic metabolic response in golden-mantled ground squirrels to determine whether the shift in thermoregulatory set point (T(set)) and subsequent fall in body temperature (T(b)) and metabolic rate observed in small mammals were greater in a species that routinely experiences hypoxic burrows and hibernates. We measured the effects of changing ambient temperature (T(a); 6--29 degrees C) on metabolism (O(2) consumption and CO(2) production), T(b), ventilation, and heart rate in normoxia and hypoxia (7% O(2)). The magnitude of the hypoxia-induced falls in T(b) and metabolism of the squirrels was larger than that of other rodents. Metabolic rate was not simply suppressed but was regulated to assist the initial fall in T(b) and then acted to slow this fall and stabilize T(b) at a new, lower level. When T(a) was reduced during 7% O(2), animals were able to maintain or elevate their metabolic rates, suggesting that O(2) was not limiting. The slope of the relationship between temperature-corrected O(2) consumption and T(a) extrapolated to a T(set) in hypoxia equals the actual T(b). The data suggest that T(set) was proportionately related to T(a) in hypoxia and that there was a shift from increasing ventilation to increasing O(2) extraction as the primary strategy employed to meet increasing metabolic demands under hypoxia. The animals were neither hypothermic nor hypometabolic, as T(b) and metabolic rate appeared to be tightly regulated at new but lower levels as a result of a coordinated hypoxic metabolic response.

Mechanisms and Mediators of Psychological Stress-Induced Rise in Core Temperature

Despite numerous case reports on "psychogenic fever," it remains uncertain how psychological stress raises core temperature and whether the rise in core temperature is a real fever or a hyperthermia. This article reviews studies on the psychological stress-induced rise in core temperature (PSRCT) in animals with the aim to facilitate studies on the mechanisms of so-called psychogenic fever in humans. To address this question, we reviewed the mechanisms and mediators of the PSRCT and classic conditioning of the fever response in animals. The PSRCT is not due to the increased locomotor activity during stress, and the magnitude of the PSRCT is the same in warm and cold environments, indicating that it is a centrally regulated rise in temperature due to an elevated thermoregulatory "set point." The PSRCT caused by conventional psychological stress models, such as open-field stress, is attenuated by cyclooxygenase inhibitors, which block prostaglandin synthesis. On the other hand, the PSRCT elicited by an "anticipatory anxiety stress" is not inhibited by cyclooxygenase inhibitors but by benzodiazepines and serotonin Type 1A receptor agonists. The febrile response can be conditioned to neutral stimuli after paired presentation with unconditioned stimuli such as injection of lipopolysaccharide, a typical pyrogen. Most findings indicate that the PSRCT is a fever, a rise in the thermoregulatory set point. The PSRCT may occur through prostaglandin E2-dependent mechanisms and prostaglandin E2-independent, 5-HT-mediated mechanisms. The febrile response can be conditioned. Thus, these mechanisms might be involved in psychogenic fever in humans.

Effects of exercise conditioning on thermoregulatory response to anticholinesterase insecticide toxicity.

Chronic exercise conditioning has been shown to alter basal thermoregulatory processes (change in thermoregulatory set point) as well as the response to infectious fever Chlorpyrifos (CHP), an organophosphate insecticide, also affects thermoregulation, causing an acute period of hypothermia followed by a delayed fever. This study examined whether chronic exercise training in the rat alters the thermoregulatory response to CHP. Core temperature and motor activity were monitored by radiotelemetry in female Sprague-Dawley rats housed individually at an ambient temperature of 22 degrees C. The rats were either given continuous access to running wheels or housed in standard cages without wheels. The exercise group ran predominately at night. After 8 weeks, the rats were gavaged with corn oil or 15 mg/kg CHP. CHP induced a transient hypothermic response followed by a delayed fever, beginning 1 day after exposure. Relative to controls, T7 decreases were not significantly different between the exercise (1.6 degrees C) group and the sedentary (0.5 degrees C) group given CHP. The sedentary and exercise group administered CHP developed a fever the day after CHP treatment. The fever response was greater in the sedentary group and persisted for approximately 3 days post-injection. Fever of the exercise group persisted for just one-half of 1 day after CHP. It is well known that chronic exercise training improves aerobic capacity; however, trained rats were not protected from the hypothermic effects of CHP. Training did ameliorate the febrile effects of CHP. Thus, exercise training may afford protection to the toxic effects of organophosphate insecticides.

Perinatal dietary NaCl level: effect on angiotensin-induced thermal and dipsogenic responses in adult rats

We have shown previously that administration of angiotensin II (Ang II) produces an apparent decrease in thermoregulatory set point. Exposure to high salt diets either perinatally or later in life has been shown to increase pressor responsiveness to administration of Ang II, so in the present studies we examine whether high dietary NaCl would also increase the thermal responsiveness to Ang II. In the first study, we show that exposure to a basal NaCl diet (0.12%) during gestation through 4 weeks postnatally produced very large elevations in plasma renin activity (PRA) and aldosterone concentrations in the offspring. Exposure to high salt diet (3%) did not decrease the levels of these parameters below those fed mid salt diet (1%). In the second study, we show that rats raised through 4 weeks of age on basal diet, but then fed standard chow until adulthood, showed greater changes in tail skin ( T sk) and colonic ( T c) temperatures following administration of Ang II (200 μg/kg sc) than either mid- or high-salt-raised groups. In the third study, we confirmed this finding and extended it to show that rats raised on a very high salt diet (6%) also did not differ from the mid-salt group. In both studies, acute water intake measured in a separate test following administration of Ang II did not differ as a function of perinatal salt diet. In a fourth study, the period of exposure to the diets was extended from the perinatal period through adulthood and, surprisingly, there was no longer an enhanced thermal response to Ang II in basal diet rats compared with rats fed the very high salt diet. In the final study, rats raised on a regular diet but exposed only as adults to the test diets showed a nonsignificant trend toward a decreased thermal response in the basal group. Thus, dietary salt level may have opposite effects on Ang II effects on adult thermoregulation, depending on the age at the exposure.

The nitric oxide pathway is an important modulator of stress-induced fever in rats

Psychological stress evokes a number of physiological responses, including a rise in body temperature ( T b), which has been suggested to be the result of an elevation in the thermoregulatory set point, i.e., a fever. This response seems to share similar mechanisms with infectious fever. A growing number of studies have provided evidence that nitric oxide (NO) has a modulatory role in infectious fever, but no report exists about the participation of NO in stress fever. Thus, the present study aimed to verify the hypothesis that NO modulates stress fever by using restraint stress as a model. To this end, we tested the effects of the non-specific NO synthase (NOS) inhibitor N G-nitro- l-arginine methyl ester ( l-NAME) or its inactive enantiomer N G-nitro- d-arginine methyl ester ( d-NAME) on colonic T b of restrained or unrestrained rats. A rapid increase in T b was observed when animals were submitted to restraint. Intravenous (i.v.) injection of l-NAME at a dose (10 mg/kg) that caused no change in T b when administered alone significantly attenuated the elevation in T b elicited by stress, indicating that the NO pathway may mediate stress fever. Moreover, intracerebroventricular (i.c.v.) l-NAME (250 μg/μl) caused a rise in T b of euthermic animals and enhanced stress fever, supporting that NO in the central nervous system (CNS) leads to a reduction in T b and, therefore, this is unlikely to be the site where NO may mediate stress fever. Taken together, these data indicate that the NO pathway plays an important role in modulating restraint stress-induced fever in rats.

Antipyretic effect of arginine vasotocin in toads.

Arginine vasotocin (AVT) is a nonmammalian analog of the mammalian hormone arginine vasopressin (AVP). These peptides are known for their antidiuretic and pressor effects. More recently, AVP has been recognized as an important antipyretic molecule in mammals. However, no information exists about the role of AVT in febrile ectotherms. We tested the hypothesis that AVT is an antipyretic molecule in the toad Bufo paracnemis. Toads equipped with a temperature probe were placed in a thermal gradient, and preferred body temperature was recorded continuously. A behavioral fever was observed after lipopolysaccharide (LPS) was injected systemically (200 microg/kg). Systemically injected AVT (300 pmol/kg) alone caused no significant change in body temperature, but abolished LPS-induced fever. Moreover, a smaller dose of AVT (10 pmol/kg), which did not affect LPS-induced fever when injected peripherally, abolished fever when injected intracerebroventricularly. We therefore conclude that AVT plays an antipyretic role in the central nervous system, by means of behavior, in an ectotherm, a fact consistent with the notion that AVT/AVP elicits antipyresis by reducing the thermoregulatory set point.

Role of nitric oxide in hypoxic hypometabolism in rats.

Because it has been recently suggested that nitric oxide (NO) may mediate the effects of hypoxia on body temperature and ventilation, the present study was designed to assess more completely the effects of a neuronal NO synthase inhibitor (7-nitroindazole, 25 mg/kg ip), at ambient temperature of 26 and 15 degrees C, on the ventilatory (V), metabolic (O(2) consumption), and thermal changes (colonic and tail temperatures) induced by ambient hypoxia (fractional inspired O(2) of 11%) or CO hypoxia (fractional inspired CO of 0.07%) in intact, unanesthetized adult rats. At both ambient temperatures, 7-nitroindazole decreased oxygen consumption, colonic temperature, and V in normoxia. The drug reduced ambient or CO hypoxia-induced hypometabolism and ventilatory response, but the hypothermia persisted. It is concluded that NO arising from neural NO synthase plays an important role in the control of metabolism and V in normoxia. As well, it mediates, in part, the hypometabolic and the ventilatory response to hypoxia. The results are consistent with the notion that central nervous system hypoxia resets the thermoregulatory set point by decreasing brain NO.

Selective brain cooling and thermoregulatory set-point.

During heat stress, the function of selective brain cooling puts trunk core temperature in an open-loop situation. As a result, trunk core temperature deviates more than expected, while brain temperature remains lower than trunk temperature. Such an influence of selective brain cooling might explain why the set-point for temperature regulation was considered to be reset at higher values in various circumstances. In the present article it is argued that during muscular exercise and dehydration the set-point is not raised when core temperature is recorded on the tympanic membrane. During fever the set-point is raised less than would be expected from readings of rectal temperature. Data from experiments on humans are used to support and illustrate the claims.

Homeostatic and Circadian Control of Body Temperature in the Fat-Tailed Gerbil

The interplay of homeostasis and circadian rhythmicity in the control of body temperature was studied in the fat-tailed gerbil ( Pachyuromys duprasi). In a first study, the body temperature rhythm of 8 gerbils maintained at 24°C under a 14L:10D light-dark cycle was studied by telemetry. Data from 9 other species of small mammals were also obtained for comparison. The gerbils were found to exhibit a robust rhythm of body temperature (the most robust of the 10 species) with a high plateau during the dark phase of the light-dark cycle and a low plateau during the light phase. In a second experiment, 5 gerbils were allowed to select the temperature of their environment by moving along a thermal gradient. The animals consistently selected higher ambient temperatures during the light phase of the light-dark cycle (when their body temperature was at the low plateau). In a third experiment, the metabolic response of 8 gerbils to an acute cold exposure was determined by indirect calorimetry. Greater cold-induced thermogenesis was observed during the light phase. The fact that the animals selected higher ambient temperatures and displayed greater cold-induced thermogenesis when their body temperature was lower contradicts the hypothesis that the body temperature rhythm is caused by a rhythmic oscillation of the thermoregulatory set point.

Ontogeny of thermoregulation during the prenatal period in birds.

In contrast to the well-known thermoregulatory processes in the postnatal period the ontogeny of the thermoregulatory effector system as well as the central nervous control elements in the prenatal period is underinvestigated. Because of this, the aim of this paper is to characterize the development of thermoregulatory mechanisms in the embryonic period of one avian species, the Muscovy duck, Cairina moschata. The experiments were carried out in three series. In the first the influence of low ambient temperatures on call producing activity was investigated, in the second the oxygen consumption of single or pooled embryos was measured in the temperature range between 34.0 and 40.5 degrees C and in the last oxygen consumption, colonic temperature and preferred temperature were examined in birds incubated in reduced temperatures (34.5 degrees C) during the last 7 days before hatching. The results of experiments led to the conclusion, that (1) some days before hatching temperature perception is very well developed, (2) endothermic reactions occur in the last quarter of embryonic development, (3) the thermoregulatory setpoint is adjustable during the perinatal period. Altogether, embryos of the Muscovy duck show in the last days of incubation typical endothermic reactions. They activate the heat production as well as the heat loss mechanisms to control the body temperature. Besides this, when vocalization is used, behavioral thermoregulatory mechanisms support the autonomic reactions.

Interactions among metabolic rate, hypoxia, and control of breathing

This review attempts to emphasize the fact that the interpretation of the ventilatory response to hypoxia may be complicated by the reduction in metabolic rate that is often associated with hypoxia. The hypoxic hypometabolism is more apparent when oxygen consumption is relatively high, either in small or young mammals at subnormal ambient temperatures or in larger mammals exposed to cold. This hypometabolism is not mediated by an activation of the arterial chemoreceptors and, furthermore, may result from a decrease in arterial oxygen content independent of the arterial PO2. Substantial experimental evidence supports the hypothesis of a lowering of the thermoregulatory set point during hypoxia through a direct action on central neural structures. The ventilatory response to hypoxia, which may appear blunted or depressed, especially in small animals exposed to cold, should in fact be reevaluated by taking into account the hypometabolism and hypothermia associated with hypoxia. Finally, it is emphasized that the mechanisms involved in control of body temperature and those that account for the interactions with hypoxia are located in the hypothalamus. This suggests that common integrative structures are probably involved in the metabolic and ventilatory responses to hypoxia.

Hormonal secretion patterns but not autonomic effector responses elicited by hypothalamic heating and cooling are altered in febrile rabbits

The effects of hypothalamic heating and cooling on thermoregulatory effector activities, lipid and carbohydrate metabolism, insulin, glucagon, thyroxine, arginine vasopressin (AVP) and cortisol were investigated in conscious rabbits and compared with those obtained in the febrile state. The study shows that under control conditions hypothalamic heating lowers, and cooling raises core temperature. Core temperature always rose to similar degrees in response to bacterial lipopolysaccharide (LPS) during an observation time of 150 min, but it started to rise from lower and higher levels, respectively, during hypothalamic heating and cooling. The effects of hypothalamic thermal stimulation on specific thermoregulatory effector activities support the conclusion that, within 60 min after LPS, the hypothalamic warm signal input is reduced relative to the cold signal input. The increase of thyroxine levels following LPS suggests that the elevation of the thermoregulatory setpoint was caused by an increased input of hypothalamic TRH neurons, known to induce the full autonomic pattern of cold defense also in response to non-thermal stimuli. With the exception of an increase of glucagon during hypothalamic cooling at control conditions, hypothalamic thermal stimulation alone did not alter lipid and carbohydrate metabolism, insulin, thyroid hormone, AVP and cortisol secretion. A spontaneous heat loss effector response separated the first from the second fever phase 60 min after LPS. Subsequently AVP and cortisol plasma levels rose in febrile animals, irrespective of hypothalamic heating and cooling, presumably as a consequence of pyrogenic activation of corticotropin releasing factor (CRF) producing neurons and their reciprocal interaction with TRH neurons on the one hand, and by a reciprocal interaction of the latter with AVP neurons on the other.

Sleep deprivation in rats with preoptic/anterior hypothalamic lesions

Chronic total sleep deprivation (TSD) of rats by the disk-over-water method reliably produces initial increases and subsequent decreases in waking intraperitoneal ( T ip ) and hypothalamic ( T hy ) temperatures, progressive increases in energy expenditure, skin lesions on the tail and plantar surfaces, debilitated appearance, and eventual death. We investigated the possible role of the preoptic/anterior hypothalamus (POAH) in the mediation of the TSD effects by comparing these effects in POAH-lesioned and unlesioned rats. Bilateral POAH lesions sufficient in size to impair homeothermic responses to changes in ambient temperature did not produce TSD-like temperature changes under baseline ambient temperatures of 28–29°C, implying that the thermoregulatory changes produced by TSD do not result from impairment of the lesioned area. However, the possibility remains that the TSD effects are mediated by damage to POAH areas that were not lesioned. During TSD, lesioned and unlesioned rats showed similar progressive increases in energy expenditure, but the lesioned rats showed earlier, steeper, and eventually greater declines in T ip and T hy . This result suggests that in unlesioned rats the POAH may counter-regulate against, and thereby attenuate, the reduction in heat retention caused by TSD. This failure of regulation in lesioned rats is consistent with their impaired response to ambient temperature change and implies that, in unlesioned rats, some POAH thermoregulatory mechanisms continue to function normally during TSD. Lesioned rats did not show the characteristic TSD-induced early increases in T ip and T hy . This result could imply either that heat retention was so compromised that body temperatures did not rise in spite of a TSD-induced increases in thermoregulatory setpoint, or that the setpoint increase in unlesioned rats is POAH-mediated. Notwithstanding the greater T ip and T hy declines in lesioned rats, they survived the TSD procedure longer than the unlesioned rats, thus supporting previous indications that death did not result from hypothermia.

Sleep deprivation in the rat by the disk-over-water method

Chronic sleep deprivation may be required to reveal the most serious physiological consequences of sleep loss, but it usually requires strong stimulation which can obscure the interpretation of effects. The disk-over-water method permits chronic sleep deprivation of rats with gentle physical stimulation that can be equally applied to yoked control rats. A series of studies with this method has revealed little or no pathology in the control rats. The deprived rats show a reliable syndrome that includes temperature changes (which vary with the sleep stages that are lost); heat seeking behavior; increased food intake; weight loss; increased metabolic rate; increased plasma norepinephrine; decreased plasma thyroxine; an increased triiodothyronine-thyroxine ratio; and an increase of an enzyme which mediates thermogenesis by brown adipose tissue. The temperature changes are attributable to excessive heat loss and an elevated thermoregulatory setpoint, both of which increase thermoregulatory load, and the other changes are interpretable as responses to this increased load. This pattern indicates that sleep serves a thermoregulatory function in the rat. The sleep deprived rats also show stereotypic ulcerative and hyperkeratotic lesions localized to the tail and plantar surfaces of the paws, and they die within a matter of weeks; the mediation of these changes is unresolved.

Cytokines and fever.

Fever is an excellent example of neuroimmunomodulation in that mediators of immunity initiate a pathway to raise the thermoregulatory set-point, resulting in behavioral and physiological responses that increase body temperature. This rise in temperature is thought to be adaptive, facilitating host defenses. Many cytokines are endogenous mediators of fever (i.e. endogenous pyrogens), including interleukin (IL)-, 1 beta, IL-6 and others. Tumor necrosis factor-alpha may be both an endogenous pyrogen and an endogenous antipyretic or cryogen, depending on the nature of the inflammatory stimuli. Although there is evidence that cytokines within the hypothalamus initiate fever, recent findings indicate that the signal to increase these brain cytokines may be neural (i.e. from peripheral nerves), rather than humoral (i.e. circulating endogenous pyrogen).

Evaluating Temperature Regulation by Field-Active Ectotherms: The Fallacy of the Inappropriate Question

We describe a research protocol for evaluating temperature regulation from data on small field-active ectothermic animals, especially lizards. The protocol requires data on body temperatures (Tb) of field-active ectotherms, on available operative temperatures (Te, "null temperatures" for nonregulating animals), and on the thermoregulatory set-point range (preferred body temperatures, Tset). These data are used to estimate several quantitative indexes that collectively summarize temperature regulation: the "precision" of body temperature (variance in Tb, or an equivalent metric), the "accuracy" of body temperature relative to the set-point range (the average difference between Tb and Tset), and the "effectiveness" of thermoregulation (the extent to which body temperatures are closer on the average to the set-point range than are operative temperatures). If additional data on the thermal dependence of performance are available, the impact of thermoregulation on performance (the extent to which performance is enhanced relative to that of nonregulating animals) can also be estimated. A sample analysis of the thermal biology of three Anolis lizards in Puerto Rico demonstrates the utility of the new protocol and its superiority to previous methods of evaluating temperature regulation. We also discuss several ways in which the research protocol can be extended and applied to other organisms.

Ciliary neurotrophic factor is an endogenous pyrogen.

Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) following intravenous injection; CNTF fever was blocked by pretreatment with indomethacin. The fever induced by CNTF was not due to contaminating endotoxins. Increasing doses of CNTF resulted in prolongation of the fever, suggesting the subsequent induction of additional endogenous pyrogenic activity. After passive transfer of plasma obtained during CNTF-induced fever, endogenous pyrogen activity was not present in the circulation; CNTF also did not induce the endogenous pyrogens interleukin 1, tumor necrosis factor, or interleukin 6 in vitro. Nevertheless, a second endogenous pyrogen may originate within the central nervous system following the systemic injection of CNTF. Of the four endogenous pyrogens described to date (interleukin 1, tumor necrosis factor, interferon, and interleukin 6), CNTF, like interleukin 6, utilizes the cell-surface gp 130 signal-transduction apparatus.

Sleep deprivation in the rat: XVII. Effect of aspirin on elevated body temperature.

Previous studies of total sleep deprivation (TSD) in the rat have shown an elevation of waking body temperature (Tb) early in the deprivation period. TSD rats defend this rise behaviorally by selecting warm ambient temperatures and autonomically by increasing heat production, thus indicating an elevation of thermoregulatory setpoint. Prostaglandins (PGs) can elevate setpoint and Tb. To investigate whether the TSD-induced rise in setpoint and Tb was mediated by PGs, aspirin, which blocks the synthesis of PGs, was administered 100 mg/kg s.q. to 11 TSD and 13 control (TSC) rats in baseline and deprivation. During baseline, aspirin produced a nonsignificant (0.16 degrees C) rise across all rats in waking Tb. For the sampled time period, waking Tb during deprivation day 3 was significantly elevated in TSD rats (0.64 degrees C, p < 0.01) but not in TSC rats (0.27 degrees C). Aspirin was administered on deprivation day 4. It produced a fall in waking Tb in TSD rats from its deprivation-induced elevation. The difference between the response to aspirin during baseline and during deprivation was significant (-0.25 degrees C, p < 0.05) for TSD rats but not TSC rats (-0.17 degrees C). Time awake after aspirin increased significantly (16.2%, p < 0.05) during baseline and declined nonsignificantly (1.1%) during deprivation. These data imply that at least part of the rise in Tb that is characteristic of TSD is mediated by PGs. To the extent that PGD2 promotes lower Tb and sleep in rats but PGE2 has opposite effects, the results are consistent with a shift from PGD2 predominance in baseline toward PGE2 predominance during TSD.(ABSTRACT TRUNCATED AT 250 WORDS)