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: 3342693
• 负责人: KATHLEEN HELEN BERECEK
• 金额: $ 13.45万
• 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 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3342693
• 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

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.

该项目的长期目标是确定 脑血管紧张素 II (AII) 在正常心血管调节中的作用 高血压的发病机制。 我们将检验以下假设： 脑AII在高血压的发病机制中发挥作用 增加交感神经系统的活动， 降低压力反射敏感性和/或增加 血管平滑肌细胞对循环的反应性 血管活性剂。 大脑 AII 可能影响交感神经流出 通过直接影响中枢神经通路来调节压力感受反射功能 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 循环水平的能力和 皮质酮。 I. 我们将研究慢性中枢神经系统疾病的影响 卡托普利的管理对发展和维持 SHR 和 DOCA 盐治疗大鼠的高血压及其影响 这种治疗对血管反应性、压力反射敏感性的影响 和交感功能。 二.我们将测量血浆水平 对照 SHR 和卡托普利处理的 SHR 中的 VP 和皮质酮 以确定这些物质的血浆水平是否发生变化 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。 我们还将研究这些之间的相互作用 通过测量交感神经末梢的激素 去甲肾上腺素的释放。 三．我们将衡量各个方面 并判断压力感受反射功能是否发生变化 SHR 和卡托普利治疗的 SHR 的压力感受反射敏感性。 我们将 看看中央 AII 和 VP 管理对 压力反射敏感性。 最后，我们将使用推拉灌注 直接将 AII 和 VP 注射至孤束核， 压力反射弧的第一个（传入）神经元并确定 该应用程序对压力反射敏感性的影响。 四．我们将 研究显微注射 AII、VP 和 ACTH 作用于被认为参与的中枢神经区域 同情心流出。 我们将研究这些之间的相互作用 具有儿茶酚胺能神经元的肽，通过 a) 测试其 去甲肾上腺素能局部破坏后对心血管的影响 具有 6-OHDA 的神经元，b) 通过测量去甲肾上腺素的释放 将这些肽显微注射到体内后通过推拉灌注 中枢神经区域和 c) 通过研究 这些肽对发射率的微电泳应用 单个去甲肾上腺素能神经元。