EFFECT OF ESTRADIOL ON ALDOSTERONE RESPONSES AND ACTIONS

雌二醇对醛固酮反应和作用的影响

• 批准号: 6208586
• 负责人: DARREN M ROESCH
• 金额: $ 3.75万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6208586
• 关键词: adrenocorticotropic hormone; aldosterone; angiotensin II; angiotensin receptor; cardiovascular disorder therapy; corticosteroid receptors; dietary sodium; estradiol; gel mobility shift assay; gene expression; heart; hippocampus; hormone regulation /control mechanism; hormone therapy; immunocytochemistry; kidney; laboratory rat; ovariectomy; postmenopause; radioimmunoassay; radiotracer; receptor expression; secretion; tissue /cell culture

Estrogen replacement therapy significantly reduces the risk of cardiovascular disease in postmenopausal women without altering circulating angiotensin II or aldosterone. Although increasing evidence suggests estrogen decreases vascular angiotensin II receptor expression and attenuates vascular responsiveness to angiotensin II, the effect of estrogen on adrenal aldosterone responses to angiotensin II and the effect of estrogen on aldosterone actions have surprisingly not been studied. Aim 1 of this proposal will use radioligand-binding and immunohistochemical techniques to determine if estradiol alters the expression and distribution of the AT1 and AT2 subtypes of angiotensin II receptors in the rat adrenal. Aim 2 will determine the effect of estradiol on angiotensin II-induced aldosterone secretion in conscious, ovariectomized rats. Aim 3 will use rndioligand-binding, immunohistochemical, and electromobility supershift assay techniques to determine the effect of estradiol on the expression and activity of aldosterone's receptor, the mineralocorticoid receptor, in the kidney, heart, and brain. The results of these studies will reveal the influence of estradiol on adrenal aldosterone responses and actions and provide further insight into the mechanisms contributing to the well-known cardiovascular benefits of estrogen replacement therapy.

雌激素替代疗法显着降低了绝经后妇女心血管疾病的风险，而不会改变循环血管紧张素II或醛固酮。尽管越来越多的证据表明雌激素会降低血管血管紧张素II受体的表达并减轻血管紧张素II的血管反应性，但雌激素对肾上腺醛固酮对血管紧张素II的反应的影响以及雌激素对醛固酮作用的作用尚未得到研究。该提案的目标1将使用放射性结合和免疫组织化学技术来确定雌二醇是否改变了大鼠肾上腺中血管紧张素II受体的AT1和AT2亚型的表达和分布。 AIM 2将确定雌二醇对有意识的卵巢切除大鼠血管紧张素II诱导的醛固酮分泌的影响。 AIM 3将使用rndioligand结合，免疫组织化学和电动性Supershift分析技术来确定雌二醇对醛固酮受体，矿物皮质激素受体，肾脏，心脏和大脑的表达和活性的影响。这些研究的结果将揭示雌二醇对肾上腺醛固酮反应和作用的影响，并进一步了解导致雌激素替代疗法的众所周知心血管益处的机制。