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

Abstract

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.

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Acknowledgments

This study was part of the activities developed by C.S.S. for obtaining a Ph.D degree at the Joint Graduate Program in Physiological Sciences (PIPGCF) from UFSCar/UNESP. We thank Euclides Roberto Secato for his technical assistance.

Funding

This work was financially supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP: Grant 15/04849-6 to K.C.B.; Grant 15/02991-0 to M.C.A; Ph.D. fellowship 2011/19131-2 to C.S.S.; Ph.D. fellowship 2017/17278-2 to C.C-S; Ph.D. fellowship 2012/15298-2 to V.B.) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq: Grant 442560/2014-1 to L.H.G).

Author information

C.S.S., K.C.B. and M.C.A.—conception and design

K.C.B., M.C.A. and L.H.G.—financial support

C.S.S., C.C-S. and V.B.—collection and assembly of data

C.S.S., C.C-S, V.B., K.C.B. and M.C.A.—data analysis and interpretation

C.S.S., C.C-S, V.B., K.C.B., L.H.G. and M.C.A.—manuscript writing

Correspondence to Carolina da Silveira Scarpellini or Kênia Cardoso Bícego.

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All procedures were approved by the local Animal Care and Use Committee of São Paulo State University (CEUA/FCAV, Protocol Number 019288/14).

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Scarpellini, C.d., Cristina-Silva, C., Biancardi, V. et al. Hypothalamic TRPV4 channels participate in the medial preoptic activation of warmth-defence responses in Wistar male rats. Pflugers Arch - Eur J Physiol 471, 1191–1203 (2019). https://doi.org/10.1007/s00424-019-02303-1

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Keywords

  • Behavioural thermoregulation
  • Body temperature
  • HC-067047
  • GSK 2193874
  • Heat loss index
  • Oxygen consumption