Heat acclimation affects the neuromodulatory role of AngII and nitric oxide during combined heat and hypohydration stress.
We studied the effect of heat acclimation on the neuromodulatory role of angiotensin (AngII) and nitric oxide during combined heat (39 degrees C) and hypohydration (water deprivation, -10% body weight) stress. Rats were divided into control (C), short (2d-STHA) or long (30d-LTHA) acclimation (34 degrees C) groups. AngII, 7-nitroindazole (7NI)-nNOS blocker, or both were centrally administered (5 mul, bolus) under light chloroform anesthesia prior to each experimental paradigms: (1) In vivo: measurements of skin-vasodilatation (VTsh) and salivation-cooling (STsh) thresholds, and heat endurance in conscious heat/hypohydrated stressed rats; (2) expression of AT(1) and AT(2) AngII receptors and nNOS were measured in the hypothalamus (Western blot); (3) transcript levels of the coding genes were measured using real-time PCR. A synthesis of the results shows a biphasic acclimatory profile of VTsh, STsh, and transcript levels of all studied genes, with transient up/down-regulatory changes on STHA. AngII affected the physiological integrative outcome primarily during euhydration, although AT membranal changes (except in LTHA) were confined to hypohydration. 7NI had an impact during hypohydration. Evidence is provided that AngII and 7NI modulate thermoregulation primarily via AT(1) and AT(2) receptors, with predominance of AT(2) signaling following LTHA and/or hypohydration, opposing a drop in AT(1)-mediated thresholds. The final shaping of AngII signaling depends on cross-talk between nNOS and AngII receptors at both molecular and protein levels. Hypohydration induces transcriptional responses but desensitizes AngII receptors signaling, attenuating their effect on VTsh and STsh, and abolishing the beneficial thermoregulatory effects achieved by heat acclimation. nNOS, AngII receptor-independent pathway is also implicated.
Schwimmer
H
H
Division of Physiology, Hadassah School of Dental Medicine, The Hebrew University, POB 12272, Jerusalem 91120, Israel. hagitsc@pob.huji.ac.il
Gerstberger
R
R
Horowitz
M
M
D000064:Acclimatization / Q000502:physiology*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D007191:Indazoles / Q000494:pharmacology; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D008954:Models, Biological; D009569:Nitric Oxide / Q000235:genetics / Q000502:physiology*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D012472:Salivation / Q000187:drug effects / Q000502:physiology; D013312:Stress, Physiological / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014868:Water Deprivation
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007191:Indazoles; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D009569:Nitric Oxide; C080122:7-nitroindazole