Estrogen & Progesterone Effects on Orthostatic Tolerance

雌激素

• 批准号: 6759457
• 负责人: NINA STACHENFELD
• 金额: $ 31.34万
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6759457
• 关键词: aldosterone; atrial natriuretic peptide; baroreceptors; blood volume; clinical research; colloids; estrogens; female; gonadotropin releasing factor; hormone inhibitor; hormone regulation /control mechanism; hormone therapy; human subject; human therapy evaluation; hydrostatic pressure; kidney function; low salt diet; osmotic pressure; plasma; postural hypotension; posture; progesterone; protein transport; renin angiotensin system; vascular endothelium permeability; vascular resistance

DESCRIPTION (provided by applicant): Orthostastic intolerance is a dysfunction of the cardiovascular system that affects primarily young, healthy women. Diminished circulating blood volume and low peripheral resistance are primary mechanisms for orthostatic intolerance. Estrogen and progesterone modulate both plasma volume (PV) and peripheral vascular resistance (PVR). The purpose of this study is to compare PV regulation, PVR and orthostatic tolerance in women under four different hormonal conditions: when estrogen and progesterone are suppressed; when estrogen is elevated; when progesterone is elevated, and when progesterone and estrogen are elevated. The Specific Aims are: 1) To determine estrogen and progesterone modulation of extracellular fluid and protein distribution, and renal mechanisms controlling water retention. Plasma protein changes alter the colloid osmotic pressure gradient across capillaries and selectively enhance or reduce plasma volume. We hypothesize that estrogen acts on vessels to reduce vascular permeability to proteins, thereby reducing protein and fluid movement out of the vasculature and increasing PV. Moreover, we will test the hypothesis that estrogen and progesterone increase total extracellular fluid volume (ECFV) associated with renin-angiotensin-aldosterone system (RAAS)-mediated renal adjustments. Thus cardiovascular adjustments to postural changes may be improved when estrogen is elevated due to greater fluid retention and due to selective fluid retention in the plasma. We also hypothesize that PV expansion is the consequence of ECFV expansion when progesterone is increased concomitant with estrogen. High progesterone alone may reduce PV both by reducing colloid osmotic pressure gradient across capillaries and by attenuating aldosterone actions on the kidney, reducing water retention, and thus extracellular fluid and plasma volumes. 2) To test the hypothesis that estrogen-related reductions in PVR response to posture changes contribute to orthostatic intolerance in women, and progesterone antagonizes these estrogen mediated changes in PVR, helping to maintain orthostatic tolerance. These studies will define the impact of estrogen and progesterone on the interaction between blood volume and vascular resistance during orthostatic challenges, and thus may improve treatment of orthostatic intolerance in women.

描述（由申请人提供）：体位不耐受是心血管系统的一种功能障碍，主要影响年轻健康的女性。 循环血量减少和外周阻力低是体位不耐受的主要机制。 雌激素和孕激素调节血浆容量 (PV) 和外周血管阻力 (PVR)。 本研究的目的是比较四种不同激素条件下女性的 PV 调节、PVR 和直立耐受性：雌激素和孕激素受到抑制时；雌激素和孕激素受到抑制时；当雌激素升高时；当孕酮升高时，以及当孕酮和雌激素升高时。 具体目标是： 1) 确定雌激素和孕激素对细胞外液和蛋白质分布的调节，以及控制水潴留的肾脏机制。 血浆蛋白的变化改变毛细血管内的胶体渗透压梯度，并选择性地增加或减少血浆容量。 我们假设雌激素作用于血管，降低血管对蛋白质的通透性，从而减少蛋白质和液体移出脉管系统并增加 PV。 此外，我们将检验以下假设：雌激素和孕激素会增加与肾素-血管紧张素-醛固酮系统（RAAS）介导的肾脏调节相关的细胞外液总量（ECFV）。 因此，当雌激素由于更大的液体潴留和血浆中的选择性液体潴留而升高时，心血管对姿势变化的调节可能会得到改善。 我们还假设，当黄体酮与雌激素同时增加时，PV 扩张是 ECFV 扩张的结果。 单独使用高孕酮可能会通过降低毛细血管中的胶体渗透压梯度和减弱醛固酮对肾脏的作用、减少水潴留以及细胞外液和血浆体积来减少PV。 2) 检验以下假设：雌激素相关的 PVR 对姿势变化的反应减少会导致女性体位不耐受，而黄体酮会拮抗这些雌激素介导的 PVR 变化，有助于维持体位耐受。 这些研究将确定雌激素和孕激素对直立性挑战期间血容量和血管阻力之间相互作用的影响，从而可能改善女性直立性不耐受的治疗。