Endothelial Deformation and Coronary Arteriolar Function

内皮变形和冠状动脉功能

• 批准号: 6420289
• 负责人: DONG SUN
• 金额: $ 25.1万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6420289
• 关键词: caveolas; cell morphology; coronary vessels; cytoskeleton; heart contraction; hemodynamics; isolation perfusion; laboratory rat; microcirculation; nitric oxide; potassium channel; tissue /cell culture; vascular endothelium; vasomotion

DESCRIPTION (provided by applicant): This is a proposal to investigate the effects of cardiac compression on the vasoactive function of the endothelium of coronary arterioles and the mechanisms underlying the endothelial deformation-induced release of NO. The endothelium of intramural coronary arterioles is constantly exposed to rhythmic compression induced by cardiac contraction, which may affect its function. My hypothesis is that endothelial cells of coronary arterioles are sensitive to cellular deformation and in response release NO to restore their original shape by dilating the vessels. This hypothesis will be tested in rats at three subsequent levels: perfused hearts, isolated coronary arterioles and cultured endothelial cells of coronary arterioles. In Specific Aim 1 in isolated and perfused heart, I aim to examine the relationship between the frequency and magnitude of cardiac compression and coronary flow. I will examine the role of NO in cardiac compression-induced increases in coronary flow and contrast the results with those obtained by flow- or myogenically-induced increases in flow. In Specific Aim 2, I plan to study the effects of vascular compression on the diameter of isolated coronary arterioles, on the release of NO, and on the myogenic response and flow-induced dilation. In Specific Aim 3, in cultured endothelial cells, I aim to monitor the changes in [Ca2+]I and the release of NO in response to endothelial deformation induced by compression, and to elucidate the correlation between [Ca2+]I and the increases in Cytosolic NO. Finally, in Specific Aim 4, I plan to investigate the possible signal transduction pathways involved in endothelial deformation-induced release of NO. The specific role of endothelial potassium channels, cytoskeleton and caveolae will be studied. I believe that the findings revealed by these studies will demonstrate a new physiologic control mechanism, namely, that cardiac contractions, by reducing arteriolar diameter and hence changing the shape of endothelial cells enhance the release of NO, which then participates in the regulation of coronary blood flow.

描述（由申请人提供）：这是一份调查