Brain angiotensin II modulates sympathoadrenal and hypothalamic pituitary adrenocortical activation during stress
Brain angiotensin II modulates sympathoadrenal and hypothalamic pituitary adrenocortical activation during stress
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DOI：
10.1046/j.1365-2826.1998.00182.x
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发表时间：
1998-01-01
影响因子：
3.2
通讯作者：
Aguilera, G
中科院分区：
文献类型：
--
作者：
Jezova, D;Ochedalski, T;Aguilera, G
血管紧张素II（Ang II）1型（AT（1））受体存在于控制自主神经活动和下丘脑-垂体-肾上腺（HPA）轴的大脑区域，包括下丘脑室旁核（PVN）中的CRH细胞。为了确定脑AT（1）受体是否参与应激时HPA轴和交感神经系统的激活，本研究观察了急性束缚应激对大鼠血浆中儿茶酚胺、ACTH和皮质酮以及室旁核CRH和CRH受体（CRH-R）mRNA水平的影响。在冷注射Losartan（10 μ g）后30分钟，血浆中肾上腺素、去甲肾上腺素和多巴胺的基础水平未受影响，但在Losartan处理的大鼠中，5和20分钟应激后的增加被钝化（与对照组相比，去甲肾上腺素P < 0.05，肾上腺素和多巴胺P < 0.01），基础或应激刺激的血浆ACTH和皮质酮水平不受冰冷的氯沙坦治疗的影响。使用原位杂交研究，PVN中CRH mRNA和CRH-R mRNA的基础水平在冰冷的氯沙坦治疗后没有变化，虽然氯沙坦对制动1小时后2或3小时CRH-R mRNA水平的增加没有影响，但它阻止了CRH mRNA的增加。阻断中枢AT（1）受体后，血浆儿茶酚胺反应减弱，表明制动应激期间交感肾上腺激活需要脑中的内源性Ang II，虽然血管紧张素II似乎不参与HPA轴的急性分泌反应，但它可能在调节PVN中CRH表达方面发挥作用。
Angiotensin II (Ang II) type-1 (AT(1)) receptors are present in areas of the brain controlling autonomic nervous activity and the hypothalamic-pituitary-adrenal (HPA) axis, including CRH cells in the hypothalamic paraventricular nucleus (PVN), To determine whether brain AT(1) receptors are involved in the activation of the HPA axis and sympathetic system during stress, we studied the effects of acute immobilization stress on plasma catecholamines, ACTH and corticosterone, and mRNA levels of CRH and CRH receptors (CRH-R) in the PVN in rats under central AT(1) receptor blockade by the selective antagonist, Losartan. While basal levels of epinephrine, norepinephrine and dopamine in plasma were unaffected 30 min after icy injection of Losartan (10 mu g), the increases after 5 and 20 min stress were blunted in Losartan treated rats (P < 0.05 for norepinephrine, and P < 0.01 for epinephrine and dopamine, vs controls), Basal or stress-stimulated plasma ACTH and corticosterone levels were unaffected by icy Losartan treatment, Using in situ hybridization studies, basal levels of CRH mRNA and CRH-R mRNA in the PVN were unchanged after icy Losartan, While Losartan had no effect on the increases in CRH-R mRNA levels 2 or 3 h after 1 h immobilization, it prevented the increases in CRH mRNA, The blunted plasma catecholamine responses after central AT(1) receptor blockade indicate that endogenous Ang II in the brain is required for sympathoadrenal activation during immobilization stress, While Ang II appears not to be involved in the acute secretory response of the HPA axis, it may play a role in regulating CRH expression in the PVN.