Estrogen & Progesterone Effects on Orthostatic Tolerance

雌激素

• 批准号: 6895431
• 负责人: NINA STACHENFELD
• 金额: $ 33.68万
• 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 2007-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895431
• 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）：正骨不耐症是心血管系统的功能障碍，主要影响年轻，健康的女性。 循环血容量减少和外周耐药性较低是体位不耐受的主要机制。 雌激素和孕酮调节血浆体积（PV）和周围血管耐药性（PVR）。 这项研究的目的是比较四种不同激素条件下女性的PV调节，PVR和体位耐受性：抑制雌激素和孕酮时；当雌激素升高时；当孕酮升高时，孕酮和雌激素升高时。 具体目的是：1）确定细胞外液和蛋白质分布的雌激素和孕酮调节，以及控制水位保留的肾脏机制。 等离子体蛋白的变化改变了毛细血管之间的胶体渗透压梯度，并有选择地增强或减少血浆体积。 我们假设雌激素作用于血管，以降低血管渗透性对蛋白质的渗透性，从而减少蛋白质和液体运动，从血管系统中移出并增加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）介导的肾脏调整相关的总细胞外流体体积（ECFV）。 因此，由于液体保留率更高，并且由于血浆中的选择性液保留率，可以改善对姿势变化的心血管调节。 我们还假设，当孕酮与雌激素同时增加时，PV扩展是ECFV膨胀的结果。 仅孕酮高孕酮可以通过降低毛细血管的胶体渗透压梯度以及减少醛固酮在肾脏上的作用，减少水分retention留来减少PV，从而减少醛固酮的作用，从而减少水分的渗透率，从而减少细胞外液体和血浆体积。 2）检验以下假设：PVR对姿势变化的降低与雌激素相关的降低有助于女性的体位不耐受，而孕激素拮抗了这些雌激素介导的PVR的变化，有助于维持静态耐受性。 这些研究将定义雌激素和孕激素对体位挑战期间血容量和血管抗性之间相互作用的影响，从而可以改善女性的体位不耐受治疗。