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

We investigated the central role of nitric oxide and Angll on thermoregulation in rats (Rattus norvegicus, Sabra strain,) undergoing heat-stress in euhydration or hypohydration (water deprivation, - 10% b.wgt). Experimental rats received Angll (100 pm), 7-nitroindazole-an antagonist of neuronal nitric oxide synthase (7NI-100 nm), or Angll+7NI in a 5-mul 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 degreesC) rats; (2) Western immunoblotting to detect Angll AT(1) and AT(2) 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 degreesC, hypohydration: - 0.9 +/- 0.18 degreesC, p < 0.05). Angll decreased STsh by 0.9 +/- 0.18 degreesC (p < 0.05) upon euhydration but increased it in hypohydration (+ 1.7 +/- 0.28 degreesC, p < 0.05). A novel finding was the involvement of AT(2) receptors in thermoregulation, which was more pronounced upon hypohydration. The response to NO was mediated via AT(1) and AT(2) receptors signaling, as well as independently. A synthesis of the results from all experimental paradigms suggests (1) a dominant influence (decrease) of NO on AT(1) receptors, thereby changing AT(1)/AT(2), receptor ratio and their signaling pathway; primarily upon hypohydration; (2) an influence of Angll (increase) on receptor density, more Pronounced during hypohydration, at both gene transcription and translation levels; and (3) an effect of Angll on nNOS protein levels, implying a Mutual effect of Angll and NO. (C) 2004 Elsevier B.V. All rights reserved.