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: 3342688
• 负责人: KATHLEEN HELEN BERECEK
• 金额: $ 14.48万
• 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/3342688
• 关键词: angiotensin /renin /aldosterone hypertension; angiotensin II; antihypertensive agents; baroreceptors; captopril; corticosterone; hormone regulation /control mechanism; neurochemistry; peripheral blood vessel; solitary tract nucleus; 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.

这个项目的长期目标是确定的作用