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：在这份提案中，申请者将检验假设 高血压遗传允许因素的存在必须是 仅为本背景而呈现并不足以表达 血管紧张素转换酶的主要降压作用机制 抑制物与大脑中所有存储和/或 新陈代谢或脑部所有感受器的改变。繁育 SHR和WKY对将用CAP处理，后代将 保持在CAP上，直到实验或从CAP(OFFCAP)中移除 2个月大，直到实验(5和 9个月大)。该项目分为以下几个具体项目 目标：目标1：确定病态患者是否缺乏表情 表型在后代中持续存在。目标2：确定 自发性高血压大鼠的血压降低是否导致缺乏 病态表型在后代中的表达。目标3：确定 不管是不是出生后的环境，通过化学媒介 在乳汁中分泌或心理行为因素(护理)导致 在后代中缺乏病态表型的表达。为了这些 研究，申请人将繁殖自发性高血压谁接受了短期CAP 治疗(宫内到2个月龄)和他们的后代到F4-F5 他们还将用肼来治疗自发性高血压病的大坝，以及 不同于CAP的降压药和不同于In的育成后代 子宫CAP-治疗未经治疗的SHR雌性，反之亦然， 分别进行了分析。目的4：确定抗高血压药物是否 卡托普利对与脑部改变相关或伴有脑部改变的影响 所有内容和/或新陈代谢和/或数量、亲和力或 脑部所有受体的亚型。目标5：确定是否有 CAP的降压作用与血管加压素的变化有关 (AVP)在大脑中的合成、含量、释放和/或AVP结合。 将对脑ALL和AVP进行生化表征(RIA和HPLC)， 通过分子生物学技术(Northern和狭缝杂交分析 RAS组分和所有受体亚型和AVP的mRNA)， 免疫细胞化学和功能(饮酒和升压反应 致Al and All和AVP)。放射性配基结合与放射自显影 将进行研究，以表征ALL和AVP在大脑中的结合 来自对照和CAP处理的SHR和WKY以及子代。由此得出的结论 提案应带来有关脑RAS作用的新信息 在高血压的病理生理学和在高血压中的重要因素 血管紧张素转换酶抑制剂的降压作用。