Drop In Tb Research Articles

Ammonium chloride-induced hypothermia is attenuated by transient receptor potential channel vanilloid-1, but augmented by ankyrin-1 in rodents

AimsSystemic administration of ammonium chloride (NH4Cl), an acidifying agent used in human patients and experimental conditions, causes hypothermia in mice, however, the mechanisms of the thermoregulatory response to NH4Cl and whether it develops in other species remained unknown. Main methodsWe studied body temperature (Tb) changes in rats and mice induced by intraperitoneal administration of NH4Cl after blockade of transient receptor potential vanilloid-1 (TRPV1) or ankyrin-1 (TRPA1) channels. Key findingsIn rats, NH4Cl decreased Tb by 0.4–0.8°C (p < 0.05). The NH4Cl-induced hypothermia also developed in Trpv1 knockout (Trpv1−/−) and wild-type (Trpv1+/+) mice, however, the Tb drop was exaggerated in Trpv1−/− mice compared to Trpv1+/+ controls with maximal decreases of 4.0 vs. 2.1°C, respectively (p < 0.05). Pharmacological blockade of TRPV1 channels with AMG 517 augmented the hypothermic response to NH4Cl in genetically unmodified mice and rats (p < 0.05 for both). In contrast, when NH4Cl was infused to mice genetically lacking the TRPA1 channel, the hypothermic response was significantly attenuated compared to wild-type controls with maximal mean Tb difference of 1.0°C between the genotypes (p = 0.008). Pretreatment of rats with a TRPA1 antagonist (A967079) also attenuated the NH4Cl-induced Tb drop with a maximal difference of 0.7°C between the pretreatment groups (p = 0.003). SignificanceTRPV1 channels limit, whereas TRPA1 channels exaggerate the development of NH4Cl-induced hypothermia in rats and mice, but other mechanisms are also involved. Our results warrant for regular Tb control and careful consideration of NH4Cl treatment in patients with TRPA1 and TRPV1 channel dysfunctions.

Cardiac Rhythms and Variation in Hibernating Arctic Ground Squirrels.

AbstractThe dramatic decrease in heart rate (HR) during entrance into hibernation is not a mere response to the lowering of core body temperature (Tb) but a highly regulated fall, as the decrease in HR precedes the drop in Tb. This regulated fall in HR is thought to be mediated by increased cardiac parasympathetic activity. Conversely, the sympathetic nervous system is thought to drive the increase of HR during arousal. Despite this general understanding, we lack temporal information on cardiac parasympathetic regulation throughout a complete hibernation bout. The goal of this study was to fill this gap in knowledge by using Arctic ground squirrels implanted with electrocardiogram/temperature telemetry transmitters. Short-term HR variability (root mean square of successive differences [RMSSD]), an indirect measure of cardiac parasympathetic regulation, was calculated in 11 Arctic ground squirrels. RMSSD, normalized as RMSSD/RR interval (RRI), increased fourfold during early entrance (from to , ). RMSSD/RRI peaked after HR dropped by over 90% and Tb fell by 70%. Late entrance was delineated by a decline in RMSSD/RRI while Tb continued to decrease. During arousal, HR started to increase 2 h before Tb, with a concurrent decrease in RMSSD/RRI to a new minimum. As Tb increased to a maximum during interbout arousal, HR declined, and RMSSD/RRI increased. These data suggest that activation of the parasympathetic nervous system initiates and regulates the HR decrease during entrance into hibernation and that withdrawal of parasympathetic activation initiates arousal. We conclude that cardiac parasympathetic regulation persists throughout all phases of a hibernation bout-a feature of the autonomic nervous system's regulation of hibernation that was not appreciated previously.

Body temperature patterns during pregnancy and parturition in moose

Gestation and lactation have high energetic requirements. Up to three-fourths of the gestation period in moose (Alces alces) overlaps with the food-scarce period in winter. During this period, moose deal with the limited forage resources available through hypometabolism with decreased heart rate and body temperature (Tb). Body temperature is also an indicator of oestrus, pregnancy and parturition, which is well documented in several domestic species. In this study, we sought to determine if moose displayed a similar Tb pattern during pregnancy and parturition to domesticated ruminants, and if we could detect parturition by combining Tb and activity data.We studied the Tb pattern of 30 free-ranging adult female moose (≥1.5 years old), equipped with ruminal temperature loggers and GPS collars. We documented a 0.13–0.19°C higher Tb in pregnant compared to non-pregnant moose, depending on the study area with the Tb difference increasing along a south-north gradient, and a drop in Tb and in activity when parturition was imminent. Detection of parturition was highly successful when combining Tb and activity data with an accuracy of 91.5%. Our findings demonstrate that Tb responses to pregnancy and parturition in a wild capital-breeding ruminant are similar to those of domesticated ruminants.

Functional role for preoptic CB1 receptors in breathing and thermal control

The anteroventral preoptic region (AVPO) of the hypothalamus is involved in both temperature and breathing regulation. This area densely express cannabinoid receptors type 1 (CB1) that modulate both excitatory and inhibitory synaptic transmission. However, it is still unknown if the endocannabinoid system located in the AVPO participates in breathing control and thermoregulation. Therefore, we tested the participation of CB1 in the AVPO in the modulation of ventilation and thermal control during normoxia and hypoxia. To this end, body temperature (Tb) of Wistar rats was monitored by datallogers and ventilation (VE) by whole body plethysmography before and after intra-AVPO microinjection of AM-251 (CB1 antagonist, 50 and 100 pmol) followed by 60 min of hypoxia exposure (7% O2). Intra-AVPO microinjection of the higher dose of AM-251 increased VE but did not change Tb under resting conditions. Exposure of rats to 7% of inspired oxygen evoked typical hypoxia-induced anapyrexia and hyperventilation after vehicle microinjection. The higher dose of the cannabinoid antagonist increased the hypoxia-induced hyperventilation, in the same magnitude as observed under normoxic condition, whereas the drop in Tb elicited by hypoxia was attenuated. Therefore, the present results demonstrate that the endocannabinoid system acting on CB1 receptors in the AVPO exerts a tonic inhibitory modulation on breathing but seem not be involved in thermoregulation during resting conditions. In addition, activation of CB1 receptors in the AVPO stimulate thermal response during hypoxia, reducing energetically expensive responses, such as the hypoxic hyperventilation.

Central administration of aminooxyacetate, an inhibitor of H2S production, affects thermoregulatory but not cardiovascular and ventilatory responses to hypercapnia in spontaneously hypertensive rats

Hydrogen sulfide (H2S) is classically known for its toxic effects. More recently H2S has been documented as a neuromodulator. Here we investigated the central effects of aminooxyacetate (AOA; inhibitor of the H2S-synthesizing enzyme cystathionine β-synthase, CBS) on cardiovascular, respiratory and thermoregulatory responses to hypercapnia in spontaneously hypertensive rats (SHR). To attain this goal we measured mean arterial pressure (MAP), heart rate (HR), ventilation (VE), and deep body temperature (Tb) of SHR and (normotensive) Wistar Kyoto (WKY) rats before and after microinjection of AOA (9 nmol/μL) or saline into the fourth ventricle immediately followed by 30-min hypercapnia exposure (7% inspired CO2). In saline-treated WKY rats, hypercapnia caused an increase in MAP accompanied by bradycardia, an increase in VE, and a drop in Tb. In AOA-treated WKY rats exposed to hypercapnia, the drug did not affect the increased MAP, potentiated the bradycardic response, attenuated the increased VE, and potentiated the drop in Tb. In saline-treated SHR, in comparison to the saline-treated WKY rats, hypercapnia elicited a minor, shorter-lasting increase in MAP with no changes in HR, evoked a greater increase in VE, and did not induce a drop in Tb. In AOA-treated SHR exposed to hypercapnia, the drug did not change the hypercapnia-induced cardiovascular and ventilatory responses while permitted a drop in Tb. Our findings indicate that AOA, an inhibitor of H2S production, modulates cardiorespiratory and thermoregulatory responses to hypercapnia in normotensive rats, whereas hypertension development in SHR is accompanied by suppression of the AOA effect on the cardiovascular and respiratory responses.

TRPV1 Inhibits the Ventilatory Response to Hypoxia in Adult Rats, but Not the CO₂-Drive to Breathe.

Receptors of the transient receptor potential (TRP) channels superfamily are expressed in many tissues and have different physiological functions. However, there are few studies investigating the role of these channels in cardiorespiratory control in mammals. We assessed the role of central and peripheral TRPV1 receptors in the cardiorespiratory responses to hypoxia (10% O2) and hypercapnia (7% CO2) by measuring pulmonary ventilation (), heart rate (HR), mean arterial pressure (MAP) and body temperature (Tb) of male Wistar rats before and after intraperitoneal (AMG9810 [2.85 µg/kg, 1 mL/kg]) or intracebroventricular (AMG9810 [2.85 µg/kg, 1 µL] or AMG7905 [28.5 μg/kg, 1 µL]) injections of TRPV1 antagonists. Central or peripheral injection of TRPV1 antagonists did not change cardiorespiratory parameters or Tb during room air and hypercapnic conditions. However, the hypoxic ventilatory response was exaggerated by both central and peripheral injection of AMG9810. In addition, the peripheral antagonist blunted the drop in Tb induced by hypoxia. Therefore, the current data provide evidence that TRPV1 channels exert an inhibitory modulation on the hypoxic drive to breathe and stimulate the Tb reduction during hypoxia.

Prior Exercise Training Alters the Response of White and Brown Adipose Tissue to Cold Stress

Brown adipose tissue is a thermogenic tissue bed that produces heat in conditions of cold environmental temperatures. While possessing much lower oxidative capacity than brown adipose tissue, recent findings have suggested that exercise training can increase the thermogenic capacity of white adipose tissue. What is not known is if exercise training can alter the response of an animal to cold stress. To address this question, male C57BL/6 mice were subject to either exercise training by voluntary wheel running (EX) or a sedentary (SED) intervention for 12 days. EX mice ran approximately 6km/day, which led to decreased body weight and increased glucose tolerance, while maintaining a similar pattern of food intake to SED. Mice were then further divided into groups that would be kept at room temperature (22°C) or a cold challenge of 4°C for 48‐hrs, thus we examined four groups in this study; (i) SED kept at room temperature (SRT), (ii) exercise trained kept at room temperature (EXRT), (iii) SED kept at 4°C (SC), and (iv) EX kept at 4°C (EXC). Rectal temperatures (Tb) of SC and EXC were lower than that of SRT and EXRT, and the initial drop in Tb of EXC was less than that observed in the SC 2‐hours following the start of the cold, however this difference was not maintained throughout the rest of the cold exposure. 48‐hrs of cold exposure led to reductions in body weight and epididymal and subcutaneous adipose tissue mass in the SED but not EX mice. Conversely, interscapular brown adipose tissue mass was increased following cold exposure in previously EX but not SED animals Taken together, our data demonstrates a unique effect of prior exercise on altering the response of adipose tissue to cold stress.Support or Funding InformationD.C.W. is a Tier II Canada Research Chair. This work was funded by an NSERC Discovery Grant to D.C.W.

α4-Containing nicotinic receptors contribute to the effects of perinatal nicotine on ventilatory and metabolic responses of neonatal mice to ambient cooling.

Among numerous studies, perinatal nicotine exposure (PN) has had variable effects on respiratory control in the neonatal period. The effects of acute nicotine exposure on breathing are largely mediated by α4-containing nicotine acetylcholine receptors (nAChRs). These receptors are also involved in thermoregulatory responses induced by both acetylcholine and nicotine. We therefore hypothesized that α4-containing nAChRs would mediate the effects of PN on the metabolic and ventilatory responses of neonates to modest cold exposure. Wild-type (WT) and α4 knockout (KO) mice were exposed to 6 mg·kg-1·day-1 nicotine or vehicle from embryonic day 14 At postnatal day (P) 7 mice were cooled from an ambient temperature (TA) of 32 to 20°C. Body temperature (TB), rate of O2 consumption (V̇o2), ventilation (V̇e), respiratory frequency (FB), and tidal volume (VT) were continually monitored. An absence of α4 had no effect on the metabolic response to ambient cooling. Surprisingly, PN selectively increased the metabolic response of KO pups to cooling. Regardless, KO pups became hypothermic to the same degree as WT pups, and for both genotypes the drop in TB was exacerbated by PN. PN led to hyperventilation in WT pups caused by an increase in VT, an effect that was absent in α4 KO littermates. We show that PN interacts with α4-containing nAChRs in unique ways to modulate the control of breathing and thermoregulation in the early postnatal period.

Gaseous mediators in temperature regulation.

Deep body temperature (Tb) is kept relatively constant despite a wide range of ambient temperature variation. Nevertheless, in particular situations it is beneficial to decrease or to increase Tb in a regulated manner. Under hypoxia for instance a regulated drop in Tb (anapyrexia) is key to reduce oxygen demand of tissues when oxygen availability is diminished, leading to an increased survival rate in a number of species when experiencing low levels of inspired oxygen. On the other hand, a regulated rise in Tb (fever) assists the healing process. These regulated changes in Tb are mediated by the brain, where afferent signals converge and the most important regions for the control of Tb are found. The brain (particularly some hypothalamic structures located in the preoptic area) modulates efferent activities that cause changes in heat production (modulating brown adipose tissue activity and perfusion, for instance) and heat loss (modulating tail skin vasculature blood flow, for instance). This review highlights key advances about the role of the gaseous neuromodulators nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) in thermoregulation, acting both on the brain and the periphery.

Polysaccharide peptide induces a tumor necrosis factor-α-dependent drop of body temperature in rats

Polysaccharide peptide (PSP) extracted from the Coriolus versicolor mushroom is frequently suggested as an adjunct to the chemo- or radiotherapy in cancer patients. It improves quality of the patients' life by decreasing pain, fatigue, loss of appetite, nausea, and vomiting. However, the effect of PSP on body temperature has not thus far been studied, although it is well known that treatment with other polysaccharide adjuvants, such as lipopolysaccharides, may induce fever. The aim of the present study, therefore, was to investigate the influence of PSP on temperature regulation in rats. We report that intraperitoneal injection of PSP provoked a dose-dependent decrease of temperature in male Wistar rats equipped with biotelemetry devices to monitor deep body temperature (Tb). The response was rapid (i.e., with latency of 15–20min), transient (lasting up to 5h post-injection), and accompanied by a significant elevation of the blood tumor necrosis factor-α (TNF-α) level. Pretreatment of the rats with anti-TNF-α antibody prevented the PSP-induced drop in Tb. Based on these data, we conclude that rats may develop an anapyrexia-like response to the injection of peptidopolysaccharide rather than fever, and the response was TNF-α-dependent.

Age and gender influence the cardiorespiratory function and metabolic rate of broiler chicks during normocapnia and hypercapnia

Pulmonary ventilation (V⋅E), body temperature (Tb), mean arterial pressure (MAP), heart rate (fH) and metabolic rate (V⋅O2) were measured in 10 (d10)- and 21 (d21)-day-old male and female chicks exposed to 7% CO2. Under normocapnia, V⋅E was higher in d10 chicks than in d21 due to a higher tidal volume; in females a higher respiratory frequency (fR) was also observed. The d10 birds presented higher fH and V⋅O2. The d21 females showed the highest CO2 ventilatory response due to increased fR. MAP did not change during hypercapnia while a hypercapnic bradycardia occurred, except in d21 females. Hypercapnia induced a drop in Tb in all groups and an increase in V⋅O2 in d21 males. Overall, no gender effect is observed in cardiorespiratory and metabolic variables in d10 and d21 chicks under normocapnia, the differences in V⋅E and fH between ages may be related to distinct metabolic demands of these phases. The d21 female chicks seem to be more sensitive to hypercapnia.

Hypoxic and hypercapnic ventilatory response in rats with estradiol valerate‐induced polycystic ovaries (LB773)

We evaluated pulmonary ventilation (VE) and body temperature (Tb) during hypercapnia (7%CO2) and hypoxia (7%O2) in a female rat model in which estradiol valerate (EV) (2mg/0.2mL/rat or oil (control) were administered intramuscularly in a single dose to induce Polycystic ovary syndrome (PCOS). The experiments were performed 30, 45 or 60 days after EV injection. The ovaries of 30, 45 and 60 days EV group displayed typical PCOS‐like changes. Plasma levels of estradiol (E2) and progesterone (P4) increased in 30 (E2: 74.5 ± 23.5 pg/mL; P4: 18.3 ±4.5 ng/mL), 45 (E2: 70.8 ± 17.5 pg/mL; P4: 21.3 ±7.6 ng/mL) and 60 (E2: 71.4 ± 4.7 pg/mL; P4: 23.7 ±4.5 ng/mL) days EV groups whereas testosterone (T) increased only in 45 (58.4±6.5 pg/mL) and 60 (79.5±18.3 pg/mL) days EV groups compared with control group (E2: 46.9±11.3 pg/mL; P4: 9.9±3.4 ng/mL; T: 22.6±1.9 pg/mL). 30, 45, 60 EV treatment did not affect resting ventilation and hypoxic ventilatory response. However, the increase in ventilation produced by hypercapnia was attenuated after 30 days EV group (1978.9 ± 85.7 mL.kg‐1.min‐1 in control group, 1651.2 ± 369.3 in 45 days group and 1617.4± 131.4 in 60 days group vs 771.0 ± 172.4 in 30 days group). Hypoxia induced Tb to reduce in all groups, a response that was amplified in 30 days EV group. Our results suggest that initial alterations promoted by EV treatment changes CO2‐drive to breathe and hypoxia‐induced drop in Tb, and these responses are compensated in 45 and 60 days EV females.

Acid-base balance in the developing marsupial: from ectotherm to endotherm

Marsupial joeys are born ectothermic and develop endothermy within their mother's thermally stable pouch. We hypothesized that Tammar wallaby joeys would switch from α-stat to pH-stat regulation during the transition from ectothermy to endothermy. To address this, we compared ventilation (Ve), metabolic rate (Vo2), and variables relevant to blood gas and acid-base regulation and oxygen transport including the ventilatory requirements (Ve/Vo2 and Ve/Vco2), partial pressures of oxygen (PaO2), carbon dioxide (PaCO2), pHa, and oxygen content (CaO2) during progressive hypothermia in ecto- and endothermic Tammar wallabies. We also measured the same variables in the well-studied endotherm, the Sprague-Dawley rat. Hypothermia was induced in unrestrained, unanesthetized joeys and rats by progressively dropping the ambient temperature (Ta). Rats were additionally exposed to helox (80% helium, 20% oxygen) to facilitate heat loss. Respiratory, metabolic, and blood-gas variables were measured over a large body temperature (Tb) range (∼15-16°C in both species). Ectothermic joeys displayed limited thermogenic ability during cooling: after an initial plateau, Vo2 decreased with the progressive drop in Tb. The Tb of endothermic joeys and rats fell despite Vo2 nearly doubling with the initiation of cold stress. In all three groups the changes in Vo2 were met by changes in Ve, resulting in constant Ve/Vo2 and Ve/Vco2, blood gases, and pHa. Thus, although thermogenic capability was nearly absent in ectothermic joeys, blood acid-base regulation was similar to endothermic joeys and rats. This suggests that unlike some reptiles, unanesthetized mammals protect arterial blood pH with changing Tb, irrespective of their thermogenic ability and/or stage of development.

Hydrogen sulfide as a cryogenic mediator of hypoxia-induced anapyrexia

Hypoxia causes a regulated decrease in body temperature (Tb), a response that has been aptly called anapyrexia, but the mechanisms involved are not completely understood. The roles played by nitric oxide (NO) and other neurotransmitters have been documented during hypoxia-induced anapyrexia, but no information exists with respect to hydrogen sulfide (H 2S), a gaseous molecule endogenously produced by cystathionine β-synthase (CBS). We tested the hypothesis that H 2S production is enhanced during hypoxia and that the gas acts in the anteroventral preoptic region (AVPO; the most important thermosensitive and thermointegrative region of the CNS) modulating hypoxia-induced anapyrexia. Thus, we assessed CBS and nitric oxide synthase (NOS) activities [by means of H 2S and nitrite/nitrate (NO x) production, respectively] as well as cyclic adenosine 3′,5′-monophosphate (cAMP) and cyclic guanosine 3′,5′-monophosphate (cGMP) levels in the anteroventral third ventricle region (AV3V; where the AVPO is located) during normoxia and hypoxia. Furthermore, we evaluated the effects of pharmacological modifiers of the H 2S pathway given i.c.v. or intra-AVPO. I.c.v. or intra-AVPO microinjection of CBS inhibitor caused no change in Tb under normoxia but significantly attenuated hypoxia-induced anapyrexia. During hypoxia there were concurrent increases in H 2S production, which could be prevented by CBS inhibitor, indicating the endogenous source of the gas. cAMP concentration, but not cGMP and NO x, correlated with CBS activity. CBS inhibition increased NOS activity, whereas H 2S donor decreased NO x production. In conclusion, hypoxia activates H 2S endogenous production through the CBS-H 2S pathway in the AVPO, having a cryogenic effect. Moreover, the present data are consistent with the notion that the two gaseous molecules, H 2S and NO, play a key role in mediating the drop in Tb caused by hypoxia and that a fine-balanced interplay between NOS-NO and CBS-H 2S pathways takes place in the AVPO of rats exposed to hypoxia.

Large African TB Study Reveals Powerful Strategy to Curb Disease

An ambitious study exploring two strategies to increase tuberculosis testing and treatment found that one approach led to a 22% drop in TB over 3 years, whereas the other had no effect on prevalence of the disease.

Central NO–cGMP pathway in thermoregulation and survival rate during polymicrobial sepsis

Sepsis induces production of inflammatory mediators such as nitric oxide (NO) and causes physiological alterations, including changes in body temperature (Tb). We evaluated the involvement of the central NO-cGMP pathway in thermoregulation during sepsis induced by cecal ligation and puncture (CLP), and analyzed its effect on survival rate. Male Wistar rats with a Tb probe inserted in their abdomen were intracerebroventricularly injected with 1 microL NG-nitro-L-arginine methyl ester (L-NAME, 250 microg), a nonselective NO synthase (NOS) inhibitor; or aminoguanidine (250 microg), an inducible NOS inhibitor; or 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 0.25 microg), a guanylate cyclase inhibitor. Thirty minutes after injection, sepsis was induced by cecal ligation and puncture (CLP), or the rats were sham operated. The animals were divided into 2 groups for determination of Tb for 24 h and assessment of survival during 3 days. The drop in Tb seen in the CLP group was attenuated by pretreatment with the NOS inhibitors (p < 0.05) and blocked with ODQ. CLP rats pretreated with either of the inhibitors showed higher survival rates than vehicle injected groups (p < 0.05), and were even higher in the ODQ pretreated group. Our results showed that the effect of NOS inhibition on the hypothermic response to CLP is consistent with the role of nitrergic pathways in thermoregulation.

Gaseous neurotransmitters and their role in anapyrexia

Mammals keep their body temperature (Tb) relatively constant even under a wide range of ambient temperature variation. However, in some particular situations it may be beneficial to increase or to decrease Tb. For instance, under hypoxic conditions, a regulated drop in Tb (anapyrexia) takes place which has been reported to be crucial for survival in a number of different species. This review highlights major advances in the research about nitric oxide (NO) and carbon monoxide (CO- where data are relatively less abundant), before focusing on the role played by these gaseous neuromediators in thermoregulation, under the conditions of euthermia and anapyrexia. Available data are consistent with the notion that both NO and CO, acting on the CNS, participate in thermoregulation, with NO decreasing Tb and CO increasing it. However further studies are required before definitive conclusions can be made as to their physiological mechanisms of action.

Seasonal changes in thermoregulatory responses to hypoxia in the Eastern chipmunk (Tamias striatus)

Mammalian heterotherms are known to be more tolerant of low oxygen levels than homeotherms. However, heterotherms demonstrate extreme seasonality in daily heterothermy and torpor expression. Because hypoxia depresses body temperature (T(b)) and metabolism in mammals, it was of interest to see if seasonal comparisons of normothermic animals of a species capable of hibernation produce changes in their responses to hypoxia that would reflect a seasonal change in hypoxia tolerance. The species studied, the Eastern chipmunk (Tamias striatus, Linnaeus 1758), is known to enter into torpor exclusively in the winter. To test for seasonal differences in the metabolic and thermoregulatory responses to hypoxia (9.9 kPa), flow-through respirometry was used to compare oxygen consumption, minimum thermal conductance and T(b) under fixed ambient temperature (T(a)) conditions whereas a thermal gradient was used to assess selected T(a) and T(b) in response to hypoxia, in both summer- and winter-acclimated animals. No differences were observed between seasons in resting metabolism or thermal conductance in normoxic, normothermic animals. Providing the animals with a choice of T(a) in hypoxia attenuated the hypoxic drop in T(b) in both seasons, suggesting that the reported fall in T(b) in hypoxia is not fully manifested in the behavioural pathways responsible for thermoregulation in chipmunks. Instead, T(b) in hypoxia tends to be more variable and dependent on both T(a) and season. Although T(b) dropped in hypoxia in both seasons, the decrease was less in the winter with no corresponding decrease in metabolism, indicating that winter chipmunks are more tolerant to hypoxia than summer animals.

Decreased thermoregulatory precision contributes to the hypoxic decrease in body temperature in lizards

Low oxygen induces a decrease in body temperature (Tb) in most vertebrates. This response has been attributed to a decrease in the in the Tb set‐point, protecting organs from oxygen depletion. In addition, hypoxia decreases activity levels and, therefore, the propensity to move. In ectotherms, where thermoregulation is mainly behavioural, hypoxia is, thus, expected to impact the precision of thermoregulatory control. To determine if thermoregulatory precision is indeed decreased in hypoxia, we evaluated the variability and level of thermoregulation of bearded dragons at five oxygen levels in three different experimental settings: a dynamic temperature‐choice shuttle box, a constant temperature dual‐choice shuttle box, and a thermal gradient. A significant increase in the size of the Tb range was observed at the lowest oxygen level (4% O2) in the dynamic shuttle box, but not in the thermal gradient. This was accompanied by a Tb drop of 2‐ 4°C, the drop being greatest when Tb must be actively defended. Situations that force lizards to continually choose temperatures lead to an increase in Tb variability, which is further exaggerated in hypoxia. This study reveals that a decrease in thermoregulatory precision caused by a diminished propensity to move or effect appropriate thermoregulatory responses may partially explain the lowering of Tb observed in hypoxic ectotherms.

Age specific effect of MK-801 on hypoxic body temperature regulation in rats

Hypoxic exposure produces a consistent decrease of rectal temperature (Tb), which is recognized as a potent protective response. While some of the neural mechanisms underlying this response have recently been described, it remains poorly known how these mechanisms evolve during post-natal development. We recently reported that in rat pups NMDA glutamate receptor limits Tb drop upon hypoxic exposure, an effect that has not been reported by others in adult rats. Accordingly, we tested the hypothesis that the implication of NMDA receptors on temperature control during hypoxic exposure evolves during development. To this aim, we evaluated the hypoxic (30 min - 12% O(2)) responses of Tb, metabolic rate, and ventilation in rats after injection of vehicle, or the NMDA receptor antagonist MK-801, at different ages (post-natal days 4, 10, 20 and 2-3 month-old - P4, P10, P20 and P60). MK-801 amplified the magnitude of the hypoxic-induced Tb drop in P4, P10 and P20 rats, but this effect was not apparent in adults. In P20 rats MK-801 tripled the hypoxic induced Tb drop, which was 0.5 degrees C in control and 1.4 degrees C in treated rats (p<0.0001). This effect was specific to temperature regulation, and was not accompanied by similar changes of other recorded parameters. MK-801 induced a significant decrease of the hypoxic ventilatory response in adults only. We conclude that NMDA glutamate receptor acts as a counter-regulatory factor that limits the hypoxic-induced drop of rectal temperature during post-natal development in rats.