TRPV4 Induces Warm‐Defense Responses in Non‐Genetically Modified Rats

TRPV4 is a warmth sensitive channel, suggested to act as a thermosensor but with no thermoregulatory role described in vivo (sensitive to temperatures in vitro at the range of ~24 ‐ 34ºC). Thus, we aimed at investigating which thermoeffectors are affected by TRPV4 activation in rats. To this end, we measured core body temperature (Tc), oxygen consumption and heat loss index (HLI) in male rats (290‐320g) under different ambient temperatures (Ta) after the intravenous blockade of this channel with HC‐067047. Moreover the preferred ambient temperature was assessed: i) after thermal stimulation combined with the intravenous blockage of TRPV4 with HC‐067047; and ii) after topical application of agonist RN‐1747. HC‐067047 caused an increase on Tc at Ta of 26 and 30°C (~0.65°C; p<0.05), but not at 22 and 32°C. At 26°C, HC‐067047‐induced hyperthermia was accompanied by increase in oxygen consumption (1.24 ± 0.2 mL O2 kg‐¹ min‐¹ more than the controls; p< 0.05), but no difference on HLI was observed. Furthermore, rats chemically stimulated with TRPV4 agonist leaned towards colder Tas (29°C for controls and 21°C for agonist‐treated; p< 0.05) and the cold‐seeking behaviour after thermal stimulation (28‐31°C) was inhibited by TRPV4 antagonist (24°C for controls and 28°C for antagonist‐treated; p< 0.05). Our results suggest, for the first time, that TRPV4 channel is involved in the recruitment of behavioural and autonomic warmth defense responses in order to regulate Tc. Financial Support: FAPESP