Estrogen & Progesterone Effects on Orthostatic Tolerance

描述（由申请人提供）：站立不耐受是育龄妇女心血管功能障碍的主要原因。从坐姿或躺姿到站姿的调整涉及中枢血容量和压力反射反应的整合。压力反射反应的充分性是中枢压力感受器敏感性和周围血管阻力的函数。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，但没有研究将这些变化直接与直立耐受性联系起来，而且雌二醇和黄体酮对人类直立反应的个体影响尚未被分离出来。雌激素和黄体酮对血压调节有相反的影响，雌二醇倾向于增加外周血管舒张，而黄体酮倾向于增加血管收缩。此外，雌二醇对黄体酮受体功能有重要影响；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单独和联合对压力反射功能和外周阻力的影响。在对晕厥前期进行下体负压试验的基础上，我们将受试者分为高、低直立耐受组，以测试以下具体目的：1)确定雌二醇和黄体酮对交感神经流的影响，以及对心血管、交感神经和综合压力反射功能的影响；2)确定雌二醇和孕酮对外周血流量的影响以及性激素对外周血流量的影响机制。我们期望这些研究不仅将增加我们对雌二醇和黄体酮在女性血压调节中的作用的理解，而且还可以作为改善女性站立耐受性的干预措施的基础。我们也期望这些研究的数据将为研究性激素对高血压、雷诺现象、糖尿病等外周循环受损相关疾病的影响提供基础

DESCRIPTION (provided by applicant): 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