Estrogen & Progesterone Effects on Orthostatic Tolerance

雌激素

• 批准号: 7489666
• 负责人: NINA STACHENFELD
• 金额: $ 3.23万
• 依托单位: JOHN B. PIERCE LABORATORY, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7489666
• 关键词: Age; Baroreflex; Blood Circulation; Blood Volume; Blood flow; Cardiovascular system; Data; Diabetes Mellitus; Disease; Estradiol; Estrogens; Experimental Designs; Functional disorder; Gonadal Steroid Hormones; Hormones; Human; Hypertension; Individual; Intervention; Lower Body Negative Pressure; Numbers; Peripheral; Peripheral Resistance; Play; Posture; Pressoreceptors; Presyncopes; Principal Investigator; Progesterone; Raynaud Phenomenon; Role; Testing; Vascular resistance; Vasodilation; Woman; base; blood pressure regulation; improved; peripheral blood; programs; receptor function; reproductive; response; vasoconstriction

Orthostatic intolerance is a leading cardiovascular dysfunction in women of reproductive age. The orthostatic adjustment from seated or lying to standing posture involves the integration of central blood volume and the baroreflex response. The adequacy of the baroreflex response is a function of central baroreceptor sensitivity and peripheral vascular resistance. While a number of studies have indicated that estradiol and progesterone impact aspects of the orthostatic response, no studies have related these changes directly to orthostatic tolerance, and the individual effects of estradiol versus progesterone on orthostatic responses in humans have not been isolated. Estrogens and progesterone have opposing influences on blood pressure regulation, with estradiol tending to increase peripheral vasodilation, and with progesterone tending to increase vasoconstriction. Moreover, estradiol has important effects on progesterone receptor function; thus the interaction of these hormones may also impact the orthostatic response in women. Our experimental design permits suppression followed by controlled estradiol and progesterone administration to determine the individual and combined effects of estradiol and progesterone on baroreflex function and peripheral resistance. On the basis of lower body negative pressure tests to presyncope, we will place subjects into high and low orthostatic tolerance groups in order to test the following Specific Aims: 1) to determine the estradiol and progesterone effects on sympathetic outflow, as well as cardiovagal, sympathetic and integrated baroreflex function; 2) to determine the estradiol and progesterone effects on peripheral blood flow and the mechanisms for the sex hormone effects on peripheral blood flow. We expect that these studies will not only increase our understanding of the roles estradiol and progesterone play in blood pressure regulation in women, but may also serve as a basis for interventions to improve orthostatic tolerance in women. We also expect that the data in these studies will provide a basis to study the impact of sex hormones on diseases related to compromised peripheral circulation, such as hypertension, Raynaud's phenomenon and diabetes.

直立不耐受是育龄妇女的主要心血管功能障碍。 直立式 从坐姿或卧姿到站立姿势的调整涉及中心血容量和 压力反射反应。 压力反射反应的充分性是中枢压力感受器敏感性的函数 和外周血管阻力。虽然许多研究表明雌二醇和黄体酮 影响直立反应的各个方面，没有研究将这些变化直接与直立反应联系起来 耐受性以及雌二醇与孕酮对人类直立反应的个体影响 没有被孤立。雌激素和孕激素对血压调节具有相反的影响， 雌二醇倾向于增加外周血管舒张，而黄体酮则倾向于增加 血管收缩。 此外，雌二醇对孕激素受体功能也有重要影响；因此 这些激素的相互作用也可能影响女性的直立反应。我们的实验设计 允许抑制，然后控制雌二醇和黄体酮给药以确定 雌二醇和黄体酮对压力反射功能和外周阻力的单独和联合作用。 在晕厥先兆下半身负压测试的基础上，我们将受试者分为高和低 立位耐受组，以测试以下具体目标：1) 确定雌二醇和 黄体酮对交感神经流出以及心迷走神经、交感神经和综合压力反射的影响 功能; 2) 确定雌二醇和孕酮对外周血流的影响及其机制 性激素对外周血流的影响。 我们期望这些研究不仅会增加我们的 了解雌二醇和黄体酮在女性血压调节中的作用，但可能 也可作为改善女性直立耐受力的干预措施的基础。 我们还期望数据 这些研究将为研究性激素对与受损相关的疾病的影响提供基础 末梢循环，如高血压、雷诺现象和糖尿病。