Schwimmer H, Gerstberger R, Horowitz M
Division of Physiology, Hadassah School of Dental Medicine, The Hebrew University, POB 12272, Jerusalem 91120, Israel.
Brain Res Mol Brain Res. 2004 Nov 4;130(1-2):95-108. doi: 10.1016/j.molbrainres.2004.07.011.
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.
我们研究了热适应对血管紧张素（AngII）和一氧化氮在热（39摄氏度）与低水合（缺水，体重减轻10%）联合应激过程中的神经调节作用的影响。将大鼠分为对照组（C）、短期（2天-短期热适应，STHA）或长期（30天-长期热适应，LTHA）适应（34摄氏度）组。在每次实验范式之前，于轻度氯仿麻醉下经中央给药（5微升，推注）AngII、7-硝基吲唑（7NI）-nNOS阻断剂或两者：（1）体内实验：测量清醒的热/低水合应激大鼠的皮肤血管舒张（VTsh）和唾液分泌冷却（STsh）阈值以及耐热性；（2）在下丘脑测量AT(1)和AT(2) AngII受体以及nNOS的表达（蛋白质印迹法）；（3）使用实时PCR测量编码基因的转录水平。结果综合显示，VTsh、STsh以及所有研究基因的转录水平呈现双相适应特征，在短期热适应时有短暂的上调/下调变化。AngII主要在等水合期间影响生理整合结果，尽管AT膜变化（长期热适应组除外）仅限于低水合状态。7NI在低水合期间有影响。有证据表明，AngII和7NI主要通过AT(1)和AT(2)受体调节体温，长期热适应和/或低水合后AT(2)信号占主导，对抗AT(1)介导的阈值下降。AngII信号的最终形成取决于nNOS与AngII受体在分子和蛋白质水平上的相互作用。低水合诱导转录反应，但使AngII受体信号脱敏，减弱其对VTsh和STsh的影响，并消除热适应所实现的有益体温调节作用。nNOS，即不依赖AngII受体的途径也有涉及。
