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.

确定卡托普利（CAP）的降压作用是否为 与脑血管紧张素II（AII）储存的改变有关，代谢， 或受体结合，以及血管反应性的变化Baroreflex 活动和与血压降低相关的同情语气 CAP的效果与大脑AII的变化有关。我们将执行 遵循特定目的： 目的1：检验CAP降压作用的假设 SHR与大脑AII合成的改变有关或伴随 和/或代谢和/或数量减少，亲和力或法规变化 脑AII受体的。脑AII将以生化为特征（RIA 在盖帽处理和对照方面，HPLC免疫细胞化学和功能 Shr和Wky。放射性结合研究将用于表征AII 在大脑和血管组织中结合。 AIM II：检验以下假设：SHR中的血管反应性提高 与大脑AII刺激ACTH-皮质酮和/或VP有关 CAP处理的大鼠中血管反应降低与A有关 大脑AII诱导的这些激素的释放减少。血管 反应性将在整个动物和孤立的动物中进行评估 人为地灌注肾血管床。这些研究将在 对照和帽子治疗的大鼠在高压IV或内部或之后 VP皮质酮或亚压ICV输注的动脉（IA）输注 AII或SAR（1）THR（8）AII。 AIM III：测试在SHR中重置压力感受器反射的假设 与大脑AII对神经中心的直接中心作用有关 控制反射和/或全部诱导的VP释放变化，以及 CAP诱导的增强BaroreFlex敏感性与 大脑AII机制的改变。压力反射控制心率和 交感神经活动将在对照和CAP处理的SHR中进行评估， WKY大鼠，中央机构前后AII，VP和 SAR（1）THR（8）AII。 AIM IV：检验以下假设：SHR中提高的同情语气是 与大脑AII对控制交感神经的神经中心的影响有关 流出和/或AII诱导的VP释放的改变，并且 帽子治疗的大鼠中抑郁的交感神经语调与改变有关 在大脑中所有机制。我们将评估心血管和同情心 对后下丘脑刺激的神经反应和对显微注射 AII或VP进入大脑的区域，以调节同情 控制和盖处理WKY和SHR的流出。我们还将学习中央 使用儿茶酚胺能病变和 微孔液压技术。实验将在SHR和WKY中进行 用CAP和寿命外围给药的大鼠治疗ICV 帽。