BRAIN ANGIOTENSIN II IN THE PATHOGENESIS OF HYPERTENSION

该项目的长期目标是确定 脑血管紧张素II（AII）在正常心血管调节和 高血压的发病机制。 我们将检验这个假设， 脑AII在高血压的发病机制中起作用， 增加交感神经系统的活性， 降低压力反射敏感性和/或通过增加 血管平滑肌细胞对循环的反应性 血管活性剂 脑AII可能影响交感神经流出， 通过直接作用于中枢神经通路的压力反射功能 或通过其改变加压素（VP）释放的能力， 促肾上腺皮质激素 脑AII可能影响血管平滑肌功能 通过其改变VP循环水平的能力， 皮质酮 I.我们将研究慢性中枢神经系统 开搏通的发展和维持 DOCA盐对SHR高血压的影响 血管反应性压力反射敏感性 和交感神经功能。 二.我们将测量血浆中 正常SHR和卡托普利治疗SHR的VP和皮质酮 以确定是否有这些血浆水平的变化， 荷尔蒙 我们将研究这些激素对 整个动物和离体血管床的血管反应性 准备工作 我们还将研究这些因素之间的相互作用。 激素与交感神经末梢通过测量 释放去甲肾上腺素 三.我们将全面衡量 压力反射功能，并确定是否有变化， SHR和卡托普利治疗的SHR的压力反射敏感性。 我们将 观察中央AII和VP给药对 压力反射敏感性 最后，我们将使用推拉灌注， 将AII和VP直接注入孤束核， 压力反射弧的第一（传入）神经元，并确定 这种应用对压力反射敏感性的影响。 四.我们将 研究微量注射AII、VP和 促肾上腺皮质激素进入中枢神经区域， 交感神经流出 我们将研究它们之间的相互作用 肽与儿茶酚胺能神经元的作用， 去甲肾上腺素能神经元局灶性破坏后的心血管效应 B）通过测量去甲肾上腺素的释放 通过在将这些肽微量注射到 c）通过研究以下因素的影响， 这些肽的微电泳应用对放电率的影响 单个去甲肾上腺素能神经元。

The long term objective of this project is to determine the role of brain angiotensin II (AII) in normal cardiovascular regulation and the pathogenesis of hypertension. We will test the hypothesis that brain AII plays a role in the pathogenesis of hypertension by increasing the activity of the sympathetic nervous system, decreasing baroreflex sensitivity and/or by increasing the responsiveness of the vascular smooth muscle cell to circulating vasoactive agents. Brain AII may affect sympathetic outflow and baroreflex function by a direct effect on cental neural pathways or through its ability to alter release of vasopressin (VP) and ACTH. Brain AII may affect vascular smooth muscle function through its ability to alter circulating levels of VP and corticosterone. I. We will study the effects of chronic central administration of captopril on the development and maintenace of hypertension in SHR and DOCA-salt treated rats and the effects of this treatment on vascular reactivity, baroreflex sensitivity and sympathetic function. II. We will measure plasma levels of VP and corticosterone in control SHR and captopril treated SHR to determine whether there are changes in plasma levels of these hormones. We will study the effects of these hormones on vascular reactivity in whole animal and isolated vascular bed preparations. We will also study the interaction of these hormones with the sympathetic nerve terminal by measuring the release of norepinephrine. III. We will measure all facets of baroreflex function and determine whether there are changes in baroreflex sensitivity in SHR and captopril treated SHR. We will look at the effects of central AII and VP administration on baroreflex sensitivity. Finally, we will use push-pull perfusion to directly administer AII and VP to the nucleus tractus solitarius, the first (afferent) neuron of the baroreflex arc and determine the effects of this application on baroreflex sensitivity. IV. We will study the cardiovascular effects of microinjections of AII, VP, and ACTH onto central neural areas thought to be involved in sympathetic outflow. We will study the interactions of these peptides with catecholaminergic neurons by a) testing their cardiovascular effects after focal destruction of noradrenergic neurons with 6-OHDA, b) by measuring release of norepinephrine by push-pull perfusion after microinjection of these peptides into central neural areas and c) by studying the effects of microintophoretic application of these peptides on the firing rate of single noradrenergic neurons.