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）：体位不耐受是生殖年龄妇女的主要心血管功能障碍。从座位或躺着到站立姿势的体位调节涉及中央血液体积和压力反射反应的整合。压力反射反应的充分性是中央压力感受器敏感性和周围血管阻力的函数。尽管许多研究表明雌二醇和孕激素会影响到体位反应的方面，但没有研究将这些变化直接与体位耐受性有关，雌二醇与孕激素对人类原位反应的个别影响尚未隔离。雌激素和孕激素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，并且孕酮倾向于增加血管收缩。此外，雌二醇对孕酮受体功能具有重要影响。因此，这些激素的相互作用也可能影响女性的体位反应。我们的实验设计允许抑制雌二醇和孕酮的控制，以确定雌二醇和孕酮对压力反射功能和周围耐药性的个体和综合作用。根据下半身的负压测试，我们将把受试者放入高和低的体位耐受性基团中，以测试以下特定目的：1）确定雌二醇和孕激素对交感神经流出以及心脏伏击，交感神经，交感神经和集成的BaroreFlex功能； 2）确定雌二醇和孕酮对外周血流动的影响以及性激素对外周血流动的影响。我们预计，这些研究不仅会增加我们对女性血压调节中雌二醇和孕酮在血压调节中发挥作用的理解，而且还可以作为改善女性正常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提供一个基础，以研究性激素对与受损外周循环有关的疾病的影响，例如高血压，雷诺的现象和糖尿病