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.

描述：申请人拟研究动脉粥样硬化， 雌激素对EDRF代谢的影响。他假设侧写 在动脉粥样硬化的存在下， 作为EDRF产生减少、失活或 运输，并提出了几个调查线使用完整的 小型猪和离体心脏模型。具体来说，他建议 建立内源性S-的化学身份和特征， 亚硝基硫醇物质在静息状态和响应于已知的 EDRF的刺激物;检查S-亚硝基硫醇的特性 种在冠状动脉循环的动脉粥样硬化和退化 小型猪和有意识的慢性仪器猪 模型，并将它们与异常血管运动联系起来; 内源性雌激素、17 B-雌二醇替代的影响，以及 雌激素停药对冠状动脉内皮血管功能和 高胆固醇血症猪模型中的S-亚硝基硫醇物质;以及 测试雌性猪内源性雌激素的损失 将导致血管功能和S-亚硝基硫醇的改变 生产