ATHEROSCLEROSIS AND ESTROGEN EFFECTS ON EDRF METABOLISM

动脉粥样硬化和雌激素对 EDRF 代谢的影响

• 批准号: 2519212
• 负责人: WILLIAM L DALEY
• 金额: $ 11.09万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2519212
• 关键词: atherosclerosis; disease /disorder model; estrogens; female; heart circulation; hormone therapy; hypercholesterolemia; isolation perfusion; metabolism; miniature swine; nitric oxide; remission /regression; stimulant /agonist; thiols; vasodilators; vasomotion

DESCRIPTION: The applicant proposes to study atherosclerosis and estrogen effects on EDRF metabolism. He hypothesizes that the profile of S-nitrosothiol species will change in the presence of atherosclerosis as a direct result of decreased EDRF production, inactivation, or transport, and proposes several lines of investigation using intact miniature swine and an isolated heart model. Specifically, he proposes to establish the chemical identity and characteristics of endogenous S- nitrosothiol species in the resting state and in response to known stimulants of EDRF; to examine the characteristics of S- nitrosothiol species in the coronary circulation of atherosclerotic and regressed miniature swine and in the conscious, chronically instrumented swine model, and relate them to abnormal vasomotion; to characterize the effect(s) of endogenous estrogens, 17B-estradiol replacement, and estrogen withdrawal on both coronary endothelial vasomotor function and S-nitrosothiol species in a hypercholesterolemic swine model; and to test the hypothesis that loss of endogenous estrogen in female swine will lead to alteration in both vasomotor function and S-nitrosothiol production.

申请人拟研究动脉粥样硬化和