BRAIN ANGIOTENSIN II IN THE PATHOGENESIS OF HYPERTENSION

确定卡托普利 (CAP) 的抗高血压作用是否有效 与大脑血管紧张素 II (AII) 储存、新陈代谢的改变有关， 或受体结合以及血管反应性压力反射是否发生变化 与血压降低相关的活动和交感神经张力 CAP的影响与大脑AII的变化有关。我们将开展 以下具体目标： 目标 1：检验 CAP 的抗高血压作用这一假设 SHR 与大脑 AII 合成的改变有关或伴随改变 和/或新陈代谢和/或数量减少、亲和力或改变的调节 大脑AII受体。大脑 AII 将以生化方式进行表征（RIA CAP 处理和对照中的 HPLC 免疫细胞化学和功能 SHR 和 WKY。放射性配体结合研究将用于表征 AII 结合在脑和血管组织中。 目标 II：检验 SHR 中血管反应性增加的假设 与 ACTH-皮质酮和/或 VP 的大脑 AII 刺激有关 CAP 治疗大鼠血管反应性降低与 AII 引起的大脑中这些激素的释放减少。血管 将评估整个动物和分离的动物的反应性 人工灌注肾血管床。这些研究将在 对照和 CAP 治疗的大鼠在静脉或注射抑制药之前和之后 动脉 (ia) VP 和皮质酮输注或亚加压 icv 输注 AII 或 Sar(1)Thr(8)AII。 目标 III：检验 SHR 中压力感受器反射重置的假设 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 释放变化和 CAP 诱导的压力反射敏感性增强与 大脑AII机制的改变。压力反射控制心率和 将在对照和 CAP 治疗的 SHR 和 WKY 大鼠，AII、VP 和 AII 中央给药前后 Sar(1)Thr(8)AII。 目标 IV：检验 SHR 中交感神经紧张增加的假设 与大脑 AII 对控制交感神经的神经中枢的影响有关 流出和/或 AII 引起 VP 释放的改变，并且 CAP 治疗大鼠的交感神经张力下降与一种改变有关 大脑中的所有机制。我们将评估心血管和交感神经 神经对下丘脑后部刺激和显微注射的反应 AII 或 VP 进入被认为调节交感神经的大脑区域 对照和 CAP 处理的 WKY 和 SHR 中的流出。我们也将学习中央 使用儿茶酚胺能损伤和 VP-儿茶酚胺相互作用 微离子导入技术。实验将在 SHR 和 WKY 中进行 大鼠用 CAP 治疗 ICV，并终生外周给药 CAP。

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.