BRAIN ANGIOTENSIN II IN THE PATHOGENESIS OF HYPERTENSION

脑血管紧张素 II 在高血压发病机制中的作用

• 批准号: 3342695
• 负责人: KATHLEEN HELEN BERECEK
• 金额: $ 14.21万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3342695
• 关键词: ACE inhibitors; angiotensin /renin /aldosterone hypertension; angiotensin II; antihypertensive agents; baroreceptors; captopril; corticosterone; enzyme inhibitors; hormone regulation /control mechanism; neurochemistry; neuropeptides; peripheral blood vessel; solitary tract nucleus; spontaneous hypertensive rat; vascular smooth muscle; vasopressins

To determine whether the antihypertensive effect of captopril (CAP) is related to an alteration in brain angiotensin II (AII) stores, metabolism, or receptor binding and whether changes in vascular reactivity baroreflex activity, and sympathetic tone associated with the blood pressure lowering effect of CAP are related to changes in brain AII. We will carry out the following specific aims: Aim 1: To test the hypothesis that the antihypertensive effect of CAP in SHR is related to, or accompanied by alterations in brain AII synthesis and/or metabolism and/or decreased number, affinity or altered regulation of brain AII receptors. Brain AII will be characterized biochemically (RIA and HPLC immunocytochemically and functionally in CAP-treated and control SHR and WKY. Radioligand binding studies will be used to characterize AII binding in brain and vascular tissue. Aim II: To test the hypothesis that increased vascular reactivity in SHR is related to brain AII stimulation of ACTH-corticosterone and/or VP and that the decreased vascular reactivity in CAP treated rats is relate to a diminution in brain AII-induced release of these hormones. Vascular reactivity will be assessed in the whole animal and in the isolated artificially perfused renal vascular bed. These studies will be done in control and CAP treated rats before and after subpressor iv or intra- arterial (ia) infusions of VP an corticosterone or subpressor icv infusions of AII or Sar(1)Thr(8)AII. Aim III: To test the hypothesis that baroreceptor reflex resetting in SHR is related to a direct central action of brain AII on neural centers controlling the reflex and/or an All induced alteration in VP release and that CAP induced enhancement of baroreflex sensitivity is related to alterations in brain AII mechanisms. Baroreflex control of heart rate and sympathetic activity will be assessed in control and CAP treated SHR and WKY rats, before and after central administration of AII, VP and Sar(1)Thr(8)AII. Aim IV: To test the hypothesis that increased sympathetic tone in SHR is related to an affect of brain AII on neural centers controlling sympathetic outflow and/or an AII induced alteration in VP release and that the depressed sympathetic tone in CAP treated rats is related to an alteration in brain All mechanisms. We will assess cardiovascular and sympathetic nerve responses to posterior hypothalamic stimulation and to microinjection of AII or VP into areas of the brain thought to regulate sympathetic outflow in control and CAP treated WKY and SHR. We will also study central AII and VP-catecholamine interactions using catecholaminergic lesioning and microiontophoresis techniques. Experiments will be performed in SHR and WKY rats treated icv with CAP and with lifetime peripheral administration of CAP.

目的：确定卡托普利(CAP)的降压作用是否 与脑血管紧张素II(AII)储存、代谢、 或受体结合以及血管反应性压力反射的变化 与血压降低相关的活动性和交感神经张力 CAP的作用与脑内AII的变化有关。我们将执行 以下是具体目标： 目的1：验证CAP对高血压的降压作用 自发性高血压与脑AII合成改变有关或伴随 和/或代谢和/或数量减少、亲和力降低或调节改变 脑部AII受体。脑AII将以生化(RIA)为特征 CAP治疗组和对照组的高效液相免疫细胞化学和功能 SHR和WKY。放射性配基结合研究将用于表征AII 结合在脑和血管组织中。 目的II：验证自发性高血压患者血管反应性增强的假说 与ACTH-皮质酮和/或VP的脑AII刺激有关 CAP治疗后大鼠血管反应性降低与 AII诱导的大脑中这些荷尔蒙的释放减少。血管 将评估整个动物和孤立动物的反应性。 人工灌流肾血管床。这些研究将在#年进行。 对照组和CAP治疗大鼠在减压剂静脉注射前后或内注射 动脉(Ia)输注VP、皮质酮或降压药脑室输注 全部或非典型肺炎(1)Thr(8)全部。 目的III：验证自发性高血压大鼠压力感受器反射重置的假说 与大脑AII对神经中枢的直接中枢作用有关 控制反射和/或ALL诱导的VP释放和/或 CAP诱导的压力反射敏感性增强与 大脑所有机制的改变。压力感受性反射控制心率和 交感神经活性将在对照和CAP治疗的SHR和 WKY大鼠中枢注射AII、VP和 Sar(1)Thr(8)All. 目的IV：验证自发性高血压患者交感神经张力增加的假设 与大脑AII对控制交感神经的神经中枢的影响有关 外流和/或AII引起VP释放的改变，并且 CAP治疗大鼠交感神经张力降低与一种改变有关 在大脑中所有的机制。我们将评估心血管和交感神经 神经对下丘脑后部刺激和微量注射的反应 AII或VP进入大脑中被认为调节交感神经的区域 对照组和CAP组WKY和SHR流出。我们还将学习中央 AII和VP-儿茶酚胺相互作用的儿茶酚胺能和 微离子导入技术。实验将在SHR和WKY进行 脑室注射CAP和终生外周给药的大鼠 帽子。