Hypothalamic TRPV4 channels participate in the medial preoptic activation of warmth-defence responses in Wistar male rats.

Recently, we have described, in non-genetically modified rats, that peripheral transient receptor potential vanilloid-4 (TRPV4) channels are activated and trigger warmth-defence responses at ambient temperatures of 26-30 °C. Evidence points to the presence of TRPV4 in the medial preoptic area, a region described to be involved in the activation of thermoeffector pathways, including those involved in heat loss. Thus, we tested the hypothesis that TRPV4 in the medial preoptic area modulates thermoregulation under warm conditions. To this end, under two ambient temperatures (21 and 28 °C), body temperature was measured in rats following blockade of preoptic TRPV4 with two antagonists, HC-067047 and GSK 2193874. Oxygen consumption, heat loss index and preferred ambient temperature were also determined in order to assess thermoeffector activity. Antagonism of central TRPV4 caused an increase in body temperature in rats exposed to 28 °C, but not in those exposed to 21 °C. The body temperature increase at 28 °C was accompanied by an increase in oxygen consumption and an earlier reduction of the heat loss index. In behavioural experiments, control animals previously exposed to warm ambient temperatures (28-30 °C) for 2 h selected colder temperatures in a thermogradient compared to those injected with HC-067047. Our results support the idea that preoptic TRPV4 modulates thermoregulation in a warm environment by activating both autonomic and behavioural heat loss responses. Thus, according to the present study and to that published recently by our group, the activation of warmth-defence responses by TRPV4 seems to be dependent on the activity of both peripheral and central channels.

Thermoregulatory consequences of salt loading in the lizard Pogona vitticeps.

Previous research has demonstrated that dehydration increases the threshold temperature for panting and decreases the thermal preference of lizards. Conversely, it is unknown whether thermoregulatory responses such as shuttling and gaping are similarly influenced. Shuttling, as an active behavioural response, is considered one of the most effective thermoregulatory behaviours, whereas gaping has been proposed to be involved in preventing brain over-heating in lizards. In this study we examined the effect of salt loading, a proxy for increased plasma osmolality, on shuttling and gaping in Pogona vitticeps. Then, we determined the upper and lower escape ambient temperatures (UETa and LETa), the percentage of time spent gaping, the metabolic rate (V̇O2 ), the evaporative water loss (EWL) during gaping and non-gaping intervals and the evaporative effectiveness (EWL/V̇O2 ) of gaping. All experiments were performed under isotonic (154 mmol l(-1)) and hypertonic saline injections (625, 1250 or 2500 mmol l(-1)). Only the highest concentration of hypertonic saline altered the UETa and LETa, but this effect appeared to be the result of diminishing the animal's propensity to move, instead of any direct reduction in thermoregulatory set-points. Nevertheless, the percentage of time spent gaping was proportionally reduced according to the saline concentration; V̇O2 was also decreased after salt loading. Thermographic images revealed lower head than body surface temperatures during gaping; however this difference was inhibited after salt loading. Our data suggest that EWL/V̇O2 is raised during gaping, possibly contributing to an increase in heat transfer away from the lizard, and playing a role in head or brain cooling.

Role of preoptic opioid receptors in the body temperature reduction during hypoxia.

Evidence indicates that endogenous opioids play a role in body temperature (Tb) regulation in mammals but no data exist about the involvement of the specific opioid receptors, mu, kappa and delta, in the reduction of Tb induced by hypoxia. Thus, we investigated the participation of these opioid receptors in the anteroventral preoptic region (AVPO) in hypoxic decrease of Tb. To this end, Tb of unanesthetized Wistar rats was monitored by temperature data loggers before and after intra-AVPO microinjection of the selective kappa-opioid receptor antagonist nor-binaltorphimine dihydrochloride (nor-BNI; 0.1 and 1.0 microg/100 nL/animal), the selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 cyclic (CTAP; 0.1 and 1.0 microg/100 nL/animal), and the selective delta-opioid receptor antagonist Naltrindole (0.06 and 0.6 microg/100 nL/animal) or saline (vehicle, 100 nL/animal), during normoxia and hypoxia (7% inspired O2). Under normoxia, no effect of opioid antagonists on Tb was observed. Hypoxia induced Tb to reduce in vehicle group, a response that was inhibited by the microinjection intra-AVPO of nor-BNI. In contrast, CTAP and Naltrindole did not change Tb during hypoxia but caused a longer latency for the return of Tb to the normoxic values just after low O2 exposure. Our results indicate the kappa-opioid receptor in the AVPO is important for the reduction of Tb during hypoxia while the mu and delta receptors are involved in the increase of Tb during normoxia post-hypoxia.