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)与正常心血管调节和 高血压的发病机制。我们将检验这一假设 脑AII通过以下途径在高血压发病机制中发挥作用 增强交感神经系统的活性， 降低压力反射敏感度和/或通过增加 血管平滑肌细胞对循环的反应性 血管活性物质。脑部AII可能影响交感神经流出和 压力感受性反射对中枢神经通路的直接作用 或通过改变后叶加压素(VP)的释放和 ACTH。脑血管紧张素转换酶可能影响血管平滑肌功能 通过改变循环中的VP和 皮质酮。I.我们将研究慢性中枢神经系统的影响 卡托普利对血管紧张素转换酶的开发和维持的作用 自发性高血压大鼠和DOCA-盐治疗大鼠的高血压及其影响 对血管反应性、压力感受性反射敏感性的影响 和交感神经功能。II.我们将测量血浆中 VP和皮质酮在对照SHR和卡托普利治疗中的作用 以确定血浆中这些物质的水平是否发生变化 荷尔蒙。我们将研究这些荷尔蒙对 全动物和分离血管床中的血管反应性 准备工作。我们还将研究它们之间的相互作用 荷尔蒙与交感神经末梢的关系 释放去甲肾上腺素。三、我们将全方位衡量 函数，并确定在 压力感受器反射敏感性在SHR和卡托普利治疗中的作用。我们会 看看中央AII和副总统管理对 压力反射敏感性。最后，我们将使用推拉式灌流来 孤束核直接注射AII和VP， 压力感受性反射弧的第一(传入)神经元，并确定 这种应用对压力反射敏感性的影响。四、我们会 微量注射AII、VP和Ang对心血管影响的研究 ACTH进入中枢神经区域被认为参与了 感同身受的流出。我们将研究它们之间的相互作用 通过a)测试含有儿茶酚胺能神经元的多肽 去甲肾上腺素能局部毁损对心血管的影响 6-OHDA，b)神经元对去甲肾上腺素释放的测定 通过向脑内微量注射这些多肽后的推拉灌流 中枢神经区和c)通过研究 这些多肽在放电频率上的显微电泳法应用 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.