BRAIN ANGIOTENSIN II IN THE PATHOGENESIS OF HYPERTENSION

目的：探讨开搏通（CAP）的降压作用， 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感受性反射的变化 活动和交感神经张力与血压降低有关 CAP作用与脑AII的变化有关。创新实施 具体目标如下： 目的1：验证CAP的降压作用与高血压的关系。 SHR与脑AII合成的改变有关或伴随 和/或代谢和/或数量、亲和力降低或调节改变 大脑AII受体的变化脑AII将进行生化表征（RIA 和HPLC免疫细胞化学和功能在CAP处理和对照 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。 目的II：验证SHR血管反应性增加是 与ACTH-皮质酮和/或VP的脑AII刺激相关， CAP处理大鼠血管反应性降低与 减少脑AII诱导的这些激素的释放。血管 将在整个动物和分离的 人工灌注肾血管床。这些研究将在 对照组和CAP治疗组大鼠在降压前和降压后， 动脉（ia）输注VP和皮质酮或icv降压输注 AII或Sar（1）Thr（8）AII。 目的III：验证自发性高血压大鼠压力感受性反射重调定的假说 与脑AII对神经中枢的直接中枢作用有关 控制VP释放的反射和/或All诱导的改变， CAP诱导的压力反射敏感性增强与 改变了大脑的所有机制。压力反射控制心率和 将在对照和CAP治疗的SHR中评估交感神经活性， WKY大鼠，在AII、VP和 Sar（1）Thr（8）所有 目的IV：验证自发性高血压大鼠交感神经张力增加是 与脑AII对控制交感神经中枢的影响有关 流出和/或AII诱导VP释放的改变， CAP处理大鼠的交感神经张力降低与 所有的机制。我们将评估心血管和交感神经系统 刺激下丘脑后部和微量注射的神经反应 将AII或VP注入被认为是调节交感神经系统的大脑区域 对照组和CAP治疗组WKY和SHR。我们还将研究中央 AII和VP-儿茶酚胺相互作用，使用儿茶酚胺能损伤和 微离子电渗技术。实验将在SHR和WKY中进行 大鼠icv与CAP和终身外周给药 章

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.