Estrogen & Progesterone Effects on Orthostatic Tolerance

雌激素

基本信息

批准号：
7259773
负责人：
NINA STACHENFELD
金额：
$ 48.48万
依托单位：
JOHN B. PIERCE LABORATORY, INC.
依托单位国家：
美国
项目类别：
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/7259773
关键词：
Adrenergic Agents Age Baroreflex Blood Circulation Blood Plasma Volume Blood Vessels Blood Volume Blood flow Cardiovascular system Data Diabetes Mellitus Disease Elements Elevation Estradiol Estrogens Experimental Designs Extracellular Fluid Functional disorder Gonadal Steroid Hormones Grant Hormones Human Hypertension Individual Intervention Lower Body Negative Pressure Mediating Modeling Nitric Oxide Nitric Oxide Synthase Numbers Organ Model Peripheral Peripheral Resistance Play Posture Pressoreceptors Presyncopes Progesterone Prostaglandins Raynaud Phenomenon Regulation Research Personnel Resistance Rest Role Skin Speed Testing Vascular resistance Vasodilation Woman adrenergic attenuation base blood pressure regulation improved men peripheral blood programs receptor function reproductive reproductive hormone research study response vasoconstriction

项目摘要

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

描述（由申请人提供）：直立不耐受是育龄妇女的主要心血管功能障碍。从坐姿或卧姿到站立姿势的体位调整涉及中心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，并且尚未分离出雌二醇与孕酮对人类直立反应的个体影响。雌激素和黄体酮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，然后控制雌二醇和孕酮给药，以确定雌二醇和孕酮对压力感受反射功能和外周阻力的单独和组合影响。在晕厥前的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的影响，交感神经和综合压力反射功能； 2)确定雌二醇和孕酮对外周血流的影响以及性激素对外周血流影响的机制。我们期望这些研究不仅会增加我们对雌二醇和黄体酮在女性血压调节中的作用的了解，而且还可以作为改善女性直立耐受性的干预措施的基础。我们还期望这些研究中的数据将为研究性激素对与外周循环受损相关的疾病（例如高血压、雷诺现象和糖尿病）的影响提供基础