Estrogen & Progesterone Effects on Orthostatic Tolerance

描述(由申请人提供)：立位不耐受是育龄妇女的主要心血管功能障碍。从坐位或卧位到站立姿势的立位调节涉及到中枢血容量和压力感受器反射反应的整合。压力感受器反应的充分性是中枢压力感受器敏感性和外周血管阻力的函数。虽然许多研究表明雌二醇和孕酮影响立位反应的某些方面，但还没有研究将这些变化与立位耐受性直接联系起来，而且雌二醇和孕酮对人体立位反应的个体影响也没有孤立出来。雌激素和黄体酮对血压调节有相反的影响，雌二醇倾向于增强外周血管扩张，而黄体酮倾向于增强血管收缩。此外，雌二醇对孕激素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，然后控制雌二醇和孕酮给药，以确定雌二醇和孕酮对压力感受器反射功能和外周阻力的单独和联合影响。在晕厥前的下体负压试验的基础上，我们将受试者分成高、低立位耐力组，以测试以下具体目的：1)测定雌二醇孕酮对交感神经流出的影响，以及心迷走神经、交感神经和综合压力感受器反射功能；2)确定雌二醇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。我们预计，这些研究不仅将增加我们对雌二醇和孕酮在女性血压调节中所起作用的了解，还可能成为提高女性立位耐力干预的基础。我们还预计，这些研究中的数据将为研究性激素对与周围循环受损相关的疾病的影响提供基础，如高血压、雷诺现象和糖尿病

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