BRAIN ANGIOTENSIN II IN HYPERTENSION

高血压脑血管紧张素 II

• 批准号: 2216856
• 负责人: KATHLEEN HELEN BERECEK
• 金额: $ 18.54万
• 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 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2216856
• 关键词: ACE inhibitors; angiotensin /renin /aldosterone hypertension; angiotensin II; antihypertensive agents; baroreceptors; baroreflex; captopril; corticosterone; enzyme inhibitors; hormone regulation /control mechanism; neurochemistry; neuropeptides; peripheral blood vessel; solitary tract nucleus; spontaneous hypertensive rat; vascular smooth muscle; vasopressins

DESCRIPTION: In this proposal the applicant will test the hypotheses that the presence of a hypertension genetic permissive factor must be present for this background alone is not sufficient for expression and that the major antihypertensive mechanisms of action of ACE inhibitors is related to an alteration in brain All stores and/or metabolism or to an alteration in the brain All receptor. Breeding pairs of SHR and WKY will be treated with CAP and offspring will either be maintained on CAP until experimentation or taken off CAP (OFFCAP) at 2 months of age and kept off CAP (OFFCAP) until experimentation (5 and 9 months of age). The project is divided Into the following specific aims: Aim 1: to determine whether or not lack of expression of the morbid phenotype persists in subsequent generations. Aim 2: to determine whether a reduction in blood pressure in SHR dams leads to lack of expression of the morbid phenotype in offspring. Aim 3: to determine whether or not the postnatal environment, through chemical mediators secreted in the milk or psychobehavioral factors (nursing) lead to lack of expression of the morbid phenotype in offspring. For these studies, the applicant will breed SHR who received short term CAP treatment (in utero to 2 mo of age) and their progeny out to F4-F5 generations; they will also treat SHR dams with hydralazine, an antihypertensive agent different from CAP and rear offspring from in utero CAP- treated with untreated SHR females and vice versa, respectively. Aim 4: to determine whether or not the antihypertensive effect of captopril related to or accompanied by alterations in brain All content and/or metabolism and/or decreased number, affinity or subtype of brain All receptors. Aim 5: to determine whether or not the antihypertensive effect of CAP is related to alterations in vasopressin (AVP) synthesis, content, release and/or AVP binding in the brain. Brain All and AVP will be characterized biochemically (RIA and HPLC), via molecular biology techniques (Northern and slot blot analyses of mRNA for components of the RAS and All receptor subtypes and AVP), immunocytochemically, and functionally (drinking and pressor responses to Al and All and AVP). Radioligand binding and autoradiographical studies will be performed to characterize All and AVP binding in brains from control and CAP-treated SHR and WKY and progeny. Findings from this proposal should lead to new information concerning the role of brain RAS in the pathophysiology of hypertension and the factors important in the antihypertensive action of ACE inhibitors.

描述：在此提案中，申请人将检验假设 高血压遗传允许因子的存在必须为 仅此背景就不足以表达 并且是ACE的主要降压作用机制 抑制剂与大脑的改变有关和/或 代谢或大脑改变所有受体。选育 成对的SHR和WKY将用帽子和后代对待 保持在上限上，直到实验或取下CAP（OFFCAP） 2个月大并保持限额（外部）直到实验（5和 9个月大）。该项目分为以下特定 目的：目标1：确定是否缺乏病态的表达 表型持续存在于随后的世代中。目标2：确定 SHR大坝中血压的降低是否导致缺乏 病态表型在后代的表达。目标3：确定 是否通过化学介质的产后环境 分泌在牛奶或心理因素（护理）中导致 在后代缺乏病态表型的表达。为此 研究，申请人将繁殖获得短期上限的SHR 治疗（在子宫至2个月中）及其后代到F4-F5 世代；他们还将用氢化嗪治疗SHR大坝 降压剂与帽子和后方的降压药不同 子宫盖（用未处理的SHR女性处理），反之亦然， 分别。目标4：确定是否降压 卡托普利与大脑改变或伴随的影响 所有内容和/或代谢和/或数量，亲和力或 大脑所有受体的亚型。目标5：确定是否 CAP的降压作用与加压素的改变有关 （AVP）大脑中的合成，内容，释放和/或AVP结合。 大脑和AVP将以生化为特征（RIA和HPLC）， 通过分子生物学技术（北部和插槽印迹分析 RAS和所有受体亚型和AVP的组件的mRNA， 免疫细胞化学和功能（饮酒和施加反应） 对Al和All and AVP）。放射线和自显影 将进行研究以表征大脑中的所有和AVP结合 来自对照和盖帽处理的SHR，WKY和后代。从中的发现 提案应导致有关大脑RAS作用的新信息 在高血压的病理生理学中，以及在 ACE抑制剂的降压作用。