Nitric oxide and angiotensin II: Neuromodulation of thermoregulation during combined heat and hypohydration stress

H. Schwimmer*, R. Gerstberger, M. Horowitz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

We investigated the central role of nitric oxide and AngII on thermoregulation in rats (Rattus norvegicus, Sabra strain,) undergoing heat-stress in euhydration or hypohydration (water deprivation, -10% b.wgt). Experimental rats received AngII (100 pm), 7-nitroindazole - an antagonist of neuronal nitric oxide synthase (7NI - 100 nm), or AngII+7NI in a 5-μl bolus intracerebroventricularly (i.c.v.) under light chloroform anesthesia; untreated control rats received saline or DMSO (5%). We used three experimental paradigms: (1) heat defense responses [salivation (STsh), vasodilatation (VTsh) temperature thresholds and heat-endurance] in conscious, heat-stressed (39°C) rats; (2) Western immunoblotting to detect AngII AT1 and AT2 receptors and nNOS protein expression; (3) real-time PCR to measure gene transcripts. In the in vivo experiment, 7NI decreased thermoregulatory thresholds, namely, NO had a reciprocal effect that was more pronounced during hypohydration (e.g. euhydration: STsh: -0.7±0.01°C, hypohydration: -0.9±0.18°C, p<0.05). AngII decreased STsh by 0.9±0.18°C (p<0.05) upon euhydration but increased it in hypohydration (+1.7±0.28°C, p<0.05). A novel finding was the involvement of AT2 receptors in thermoregulation, which was more pronounced upon hypohydration. The response to NO was mediated via AT 1 and AT2 receptors signaling, as well as independently. A synthesis of the results from all experimental paradigms suggests (1) a dominant influence (decrease) of NO on AT1 receptors, thereby changing AT1/AT2 receptor ratio and their signaling pathway; primarily upon hypohydration; (2) an influence of AngII (increase) on receptor density, more pronounced during hypohydration, at both gene transcription and translation levels; and (3) an effect of AngII on nNOS protein levels, implying a mutual effect of AngII and NO.

Original languageEnglish
Pages (from-to)177-189
Number of pages13
JournalBrain Research
Volume1006
Issue number2
DOIs
StatePublished - 1 May 2004

Keywords

  • AT receptor
  • AT receptor
  • Endocrine and autonomic regulation
  • nNOS
  • Osmotic and thermal regulation
  • Salivation
  • Vasodilatation

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