title: Nitric oxide and angiotensin II: neuromodulation of thermoregulation during combined heat and hypohydration stress.
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-microl 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 degrees C) rats; (2) Western immunoblotting to detect AngII 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 degrees C, hypohydration: -0.9+/-0.18 degrees C, p<0.05). AngII decreased STsh by 0.9+/-0.18 degrees C (p<0.05) upon euhydration but increased it in hypohydration (+1.7+/-0.28 degrees C, 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 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.
authors.affiliation: Division of Physiology, Hadassah School of Dental Medicine, The Hebrew University, POB 12272, Jerusalem 91120, Israel. hagitsc@pob.huji.ac.il
authors.forename: H
authors.initials: H
authors.lastname: Schwimmer
authors.forename: R
authors.initials: R
authors.lastname: Gerstberger
authors.forename: M
authors.initials: M
authors.lastname: Horowitz
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003681:Dehydration / Q000503:physiopathology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018882:Heat Stress Disorders / Q000503:physiopathology*; D007191:Indazoles / Q000494:pharmacology; D007276:Injections, Intraventricular / Q000379:methods; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012472:Salivation / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D004791:Enzyme Inhibitors; D007191:Indazoles; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D009569:Nitric Oxide; D019808:Losartan; C080122:7-nitroindazole