CARDIOVASCULAR CONSEQUENCES OF MENOPAUSE

拟议的项目将研究更年期对 心血管系统 血管内皮细胞在 控制心血管系统通过生产各种 影响血管收缩的血管活性物质，包括 内皮素-1（ET-1）和血管舒张，包括一氧化氮（NO）。 ET-1和NO系统均表现出与年龄相关的变化， 性激素，这表明这两个系统可以改变， 绝经后雌激素缺乏症 有待检验的一般假设是，生殖系统老化 在女性，特别是绝经期，改变了血管控制机制， 内皮导致血管扩张剂减弱， 血管收缩剂对血管的影响。这些改变 使绝经后妇女易患心血管疾病。 长期目标是：（a）确定旁分泌和自分泌 血管内皮的控制机制， 绝经期和（B）建立预防和/或 治疗干预。 具体目标是：1：确定绝经相关的改变， NO系统的内皮介导的血管舒张机制。2：向 定义绝经相关的内皮机制改变- 通过ET-1系统介导的血管收缩。 研究将在未使用激素的绝经后妇女中进行 年龄在45-55岁之间的替代和绝经前妇女， 绝经后内皮NO的血管舒张作用降低， 绝经后ET-1的血管收缩作用增强。 研究将 应用在体皮内微透析结合血流 通过激光多普勒血流仪进行测量。

The proposed project will examine the effects of menopause on the cardiovascular system. Endothelial cells play a pivotal role in controlling the cardiovascular system by production of a variety of vasoactive substances that effect vasoconstriction, including endothelin-1 (ET-1), and vasodilation, including nitric oxide (NO). Both the ET-1 and NO systems show age-related changes and are influenced by sex hormones, suggesting that the two systems can be altered by estrogen deficiency after menopause. The general hypothesis to be tested is that reproductive system aging in women, specifically menopause, alters vascular control mechanisms of the endothelium resulting in attenuated vasodilator and exaggerated vasoconstrictor influences on blood vessels. These alterations predispose postmenopausal women to cardiovascular diseases. Long-term objectives are: (a) to define the paracrine and autocrine control mechanisms of the vascular endothelium that are altered by menopause and (b) to establish rationale for preventative and/or therapeutic interventions. Specific aims are: 1: To define menopause-related alterations in mechanisms of endothelium-mediated vasodilation by the NO system. 2: To define menopause-related alterations in mechanisms of endothelium- mediated vasoconstriction by the ET-1 system. Studies will be done in post-menopausal women without hormone replacement and premenopausal women ages 45-55 to examine whether vasodilator effects of the endothelial NO decrease after menopause and vasoconstrictor effects of ET-1 increase after menopause. Studies will use in vivo intradermal microdialysis combined with blood flow measurements by laser-Doppler flowmetry.