ENDOTHELIUM AND VASCULAR FUNCTION

内皮和血管功能

• 批准号: 7395015
• 负责人: Gabor Kaley
• 金额: $ 177.27万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7395015
• 关键词: ENDOTHELIUM; VASCULAR; FUNCTION

DESCRIPTION (provided by applicant): This Program Project Grant application describes studies we plan to perform as a continuation of our previous projects concerned with the regulation of cardiovascular function, primarily by endothelium-derived mediators, nitric oxide and reactive oxygen species. The present application builds on our previously obtained data to further establish the role of these agents in the control of vascular and cardiac function. Our overall hypothesis that we aim to test is that oxygen radical species, derived through activation of Nox oxidases in the vessel wall, by causing a reduction in nitric oxide bioavailability, hasten the development of vascular dysfunction leading to disease. In the first Project, Dr. Wolin will characterize how Nox-linked signaling mechanisms affect vascular function and how these mechanisms are altered in pathophysiologic conditions. In the second Project, Dr. Hintze will examine in mice, rats and dogs the role of NADPH oxidase in the increased oxidant production secondary to sodium restriction, a state associated with increased angiotensin production. He will also determine in the dog heart the effects of sodium restriction on NO dependent regulation of the coronary circulation as well as the fate of substrates and the alteration in the expression of metabolic enzymes. In the third Project, Dr. Kaley plans to study the effects of aging on vascular function in type 2 diabetic (db/db) and eNOS-KO mice, two different models of metabolic syndrome, each of which is characterized by increased oxidant stress and a reduction in nitric oxide bioavailability. The projects will be supported by three cores; one led by Dr. Edwards, providing genotyping of and physiologic measurements in mice, one led by Dr. Ungvari who will provide expertise in imaging ROS in vessels and tissues by state of the art methods and one led by Dr. Ojaimi, who will interpret data obtained by gene array techniques. We believe that our research will provide conceptual advances that will likely lead to a better understanding of the development of vascular dysfunction in disease states as well as to novel therapeutic options.

描述（由申请人提供）：该计划项目拨款申请描述了我们计划进行的研究，作为我们的延续 以前的项目涉及心血管功能的调节，主要是通过内皮衍生的 介质、一氧化氮和活性氧。目前的应用程序建立在我们之前的基础上 获得的数据进一步确定了这些药物在控制血管和心脏功能中的作用。我们的 我们旨在测试的总体假设是，通过激活 Nox 衍生的氧自由基物种 血管壁中的氧化酶通过导致一氧化氮生物利用度降低，加速了 血管功能障碍导致疾病。在第一个项目中，Wolin 博士将描述 Nox 相关信号传导如何 影响血管功能的机制以及这些机制在病理生理条件下如何改变。 在第二个项目中，Hintze 博士将在小鼠、大鼠和狗身上检查 NADPH 氧化酶在增加 继发于钠限制的氧化剂产生，这是一种与血管紧张素增加相关的状态 生产。他还将确定限制钠摄入对狗心脏中一氧化氮依赖性的影响 冠状循环的调节以及底物的命运和表达的改变 代谢酶。在第三个项目中，Kaley 博士计划研究衰老对 2 型血管功能的影响 糖尿病 (db/db) 和 eNOS-KO 小鼠，两种不同的代谢综合征模型，每种模型 其特征是氧化应激增加和一氧化氮生物利用度降低。这些项目将是 由三个核心支持；由爱德华兹博士领导的一个项目，提供以下疾病的基因分型和生理测量 小鼠，由 Ungvari 博士领导，他将根据血管和组织中 ROS 的状态提供成像专业知识 艺术方法和由 Ojaimi 博士领导的一项方法，他将解释通过基因阵列技术获得的数据。我们 相信我们的研究将提供概念上的进步，这可能会导致更好地理解 疾病状态下血管功能障碍的发展以及新的治疗选择。