RENIN-ANGIOTENSIN SYSTEM AND INJURY

肾素-血管紧张素系统和损伤

• 批准号: 2141064
• 负责人: KENNETH E BERNSTEIN
• 金额: $ 22.34万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2141064
• 关键词: DNA footprinting; angiotensin /renin /aldosterone hypertension; aorta; complementary DNA; disease /disorder model; environmental stressor; gene expression; genetic promoter element; genetic transcription; heart; hormone receptor; hormone regulation /control mechanism; kidney; laboratory mouse; laboratory rat; nucleic acid sequence; peptidyl dipeptidase A; tissue /cell culture; transfection; vascular endothelium; vascular smooth muscle

High blood pressure is epidemic among the American population; it is estimated that in excess of 30 million people are afflicted with hypertension and another 20 to 30 million suffer from borderline hypertension. Our work has focused on understanding the operation of the RAS, especially the roles of angiotensin converting enzyme (ACE) and the biology of the angiotensin II receptor. During the last four years, we have studied the regulated expression of ACE and the receptor for angiotensin II. Our desire has been twofold, to understand the biochemical control mechanisms that the RAS uses to respond to environmental change and to understand tissue specific expression of the individual components of this system. We believe these questions are central to the workings of the RAS, and thus are of major importance in blood pressure control. In the present application, we propose to continue study of ACE expression and to focus on endothelium as a tissue central to RAS action. Finally, we propose to extend these studies into understanding how the RAS responds in a well defined model of hypertension. We propose to study a model of high renin hypertension in the rat induced by surgical banding of the abdominal aorta. This model has a well defined pathophysiology; we hypothesize that part of the pathophysiologic responses to hypertension in this model are the result of changes in components of the renin-angiotensin system. Analysis of the model will allow us to correlate the observation of Specific Aims 1 (the study of ACE by the kidney and vascular smooth muscle) and Specific Aim 2 (the study of ACE expression by endothelial cells) with an in vivo example of hypertensive injury. Thus, we will investigate tissue specific gene expression and use this to understand hypertensive injury.

高血压是美国人群的流行；这是 据估计，超过3000万人遭受了 高血压和另外20至3000万的边界遭受 高血压。 我们的工作重点是了解 RA，尤其是血管紧张素转化酶（ACE）的作用和 血管紧张素II受体的生物学。 在过去的四年中，我们 已经研究了ACE的调节表达和受体 血管紧张素II。 我们的愿望是双重的，以了解 RAS用来响应的生化控制机制 环境变化并了解组织特异性表达 该系统的个别组件。 我们相信这些问题是 RAS运作的核心，因此很重要 血压控制。 在本申请中，我们建议 继续研究ACE表达并专注于内皮作为组织 RAS动作的中心。 最后，我们建议将这些研究扩展到 了解Ras在定义明确的模型中的响应 高血压。 我们建议研究一种高肾素高血压模型 大鼠由腹主动脉的手术带诱导。 这个模型 具有明确的病理生理学；我们假设 在此模型中，对高血压的病理生理反应是结果 肾素 - 血管紧张素系统组件的变化。 分析 该模型将使我们能够关联特定目的的观察1 （肾脏和血管平滑肌研究ACE）和特定 AIM 2（由内皮细胞研究ACE表达）用体内 高血压损伤的例子。 因此，我们将研究组织 特定的基因表达并使用它来了解高血压损伤。