Role of hypothalamic TRPV4 channels in activation/inhibition of autonomic thermoeffectors during fever and endotoxemic chock

Abstract

The TRPV4 are non-noxious temperature-sensitive channels, important to peripheral temperature sensation. It has been described that TRPV4 are expressed in the preoptic area of hypothalamus, a key region involved in thermoregulation. Although ther is evidence of increasing endotoxin-induced TRPV4 expression in hypothalamus of rats, no study has verified the role of these channels in the regulation of body temperature (Tb) during endotoxemia. Endotoxemia can induce increase in the Tb, i.e., fever or reduction of Tb during septic shock. Autonomic and behavioural heat gain mechanisms are activated during the development of fever and heat loss is inhibited, whereas to septic shock occurs the opposite mechanism seems to ensue. In the present study it will be investigated if the TRPV4 channels of medial preoptic area (MPO) plays a role in the activation of autonomic (thermogenesis and dry heat loss) and/or behavioural (preferred ambient temperature) thermoeffector responses during fever and septic shock induced by LPS (endotoxin). The influence of ambient temperature (Ta) on autonomic thermoeffectors will be investigated as well. To this end it will be performed the following protocols: 1 - the effect of HC-067047 microinjection, TRPV4 selective antagonist, in the MPO on Tb, oxygen consumption (thermogenesis) and heat loss index of rats submitted to intra-peritoneal (i.p) injection of LPS at Ta below the range of peripheral TRV4 activation (~21oC). 2 - the effect of HC-067047 microinjection in the MPO on Tb, oxygen consumption and heat loss index of rats submitted to i.p. injection of LPS at Ta at the range of peripheral TRV4 activation (~29oC).