CENTRAL ANGIOTENSIN IN FLUID BALANCE AND HYPERTENSION

中枢血管紧张素在液体平衡和高血压中的作用

• 批准号: 2216116
• 负责人: MICHAEL. IAN PHILLIPS
• 金额: $ 17.67万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2216116
• 关键词: ACE inhibitors; affinity chromatography; angiotensin /renin /aldosterone hypertension; angiotensin II; antihypertensive agents; blood brain barrier; corticosteroids; disease /disorder model; electrolyte balance; gene expression; high performance liquid chromatography; hippocampus; hormone receptor; hormone regulation /control mechanism; immunochemistry; in situ hybridization; messenger RNA; molecular biology; neuropeptides; neurotransmitters; northern blottings; oncogenes; radioimmunoassay; spontaneous hypertensive rat

This grant application is to continue studies on the tissue renin- angiotensin system in hypertension. The hypothesis of this proposal is that gene expression of components of the renin-angiotensin system in localized tissues is altered in different models of hypertension independently of circulating angiotensin. and that the tissue angiotensin contributes to high blood pressure. The techniques of molecular biology and in situ hybridization, combined with direct measurements of renin- angiotensin components, will be used to test the hypothesis. One of the advantages of studying mRNA accumulation in such models is that multiple tissues can be collected in the animals at the same time. Six aims are proposed. First, tissue mRNA expression in different models of hypertension will be studied, using northern blot analysis. Probes for angiotensinogen, renin and converting enzyme will be applied, and brain, vasculature, kidney, liver, adrenal, heart and skin will be tested in one- kidney-one-clip, two-kidney-one-clip, DOCA-salt, SHR and Dahl salt- sensitive hypertensive rats and their controls. The second aim, once the pattern of tissue mRNA has been established, will be to study gene expression during the development of hypertension to test if the expression appears before blood pressure elevates or if it is a result of hypertension. In the third aim the technique of in situ hybridization will be used to locate with microscopic precision were changes are occurring in different areas of the brain and autonomic ganglia. The fourth aim is to measure levels of angiotensins and other components of the synthesis in order to test whether the mRNA accumulation represents increased synthesis. Aim five is to define the cellular localization of the mRNA, particularly in neurons versus glial cells of the CNS and sympathetic nervous system, and also endothelial cells nad LLCPK1 cells. Aim six is to study the regulation of gene expression suing hormones associated with stress. Also, angiotensin II will be tested for its role in negative feedback of mRNA expression. Studies will be carried out both in vivo and in vitro. The expression of mas-oncogene mRNA in response to angiotensin II will be studied. The goal of the project is to focus on the locus of tissue angiotensin gene expression which contributes to the development of hypertension.

该拨款申请旨在继续研究组织肾素 高血压中的血管紧张素系统。 该提案的假设是 肾素-血管紧张素系统成分的基因表达 不同高血压模型中局部组织发生改变 独立于循环血管紧张素。 并且组织血管紧张素 导致高血压。 分子生物学技术 和原位杂交，结合肾素的直接测量 血管紧张素成分，将用于检验该假设。 中的一个 在此类模型中研究 mRNA 积累的优点是 可以同时在动物体内收集组织。 六个目标是 建议的。 一、不同模型中组织mRNA的表达情况 将使用 Northern blot 分析来研究高血压。 探头用于 将应用血管紧张素原、肾素和转化酶，以及大脑、 脉管系统、肾脏、肝脏、肾上腺、心脏和皮肤将在一次中进行测试 肾一夹、二肾一夹、DOCA盐、SHR和Dahl盐- 敏感高血压大鼠及其对照。 第二个目标，一旦 组织mRNA模式已经建立，将用于研究基因 高血压发展过程中的表达，以测试该表达是否 出现在血压升高之前或由于以下原因而出现 高血压。 在第三个目标中，原位杂交技术将 用于以微观精度定位正在发生的变化 大脑和自主神经节的不同区域。 第四个目标是 测量血管紧张素和其他合成成分的水平 为了测试 mRNA 积累是否代表合成增加。 目标五是确定 mRNA 的细胞定位，特别是 在中枢神经系统和交感神经系统的神经元与神经胶质细胞中， 以及内皮细胞和 LLCPK1 细胞。 目标六是研究 利用与压力相关的激素来调节基因表达。 还， 将测试血管紧张素 II 在 mRNA 负反馈中的作用 表达。 研究将在体内和体外进行。 这 mas-oncogene mRNA 响应血管紧张素 II 的表达将 研究过。 该项目的目标是关注组织的轨迹 血管紧张素基因表达有助于发育 高血压。