CARDIOVASCULAR CONSEQUENCES OF MENOPAUSE

这项拟议的项目将研究更年期对 心血管系统。内皮细胞在以下方面发挥着关键作用 通过生产各种不同的药物来控制心血管系统 影响血管收缩的血管活性物质，包括 内皮素-1(ET-1)和血管扩张，包括一氧化氮(NO)。 ET-1和NO系统都表现出与年龄相关的变化，并受到影响 通过性激素，这表明这两个系统可以通过 绝经后雌激素缺乏症。 需要检验的一般假设是生殖系统老化 在女性，特别是更年期，改变了血管控制机制 血管内皮细胞导致血管扩张剂减弱和夸大 血管收缩药对血管的影响。这些改动 使绝经后妇女易患心血管疾病。 长期目标是：(A)界定旁分泌和自分泌 血管内皮细胞改变的调控机制 更年期和(B)建立预防性和/或 治疗性干预。 具体目标是：1：定义与更年期相关的改变 一氧化氮系统内皮细胞介导的血管扩张机制。2：至 定义与更年期相关的内皮机制的改变- ET-1系统介导的血管收缩作用。 研究将在没有激素的绝经后妇女身上进行 45-55岁更年期和绝经前妇女检查是否 绝经后血管内皮细胞NO水平降低的血管扩张作用 绝经后ET-1的血管收缩作用增强。研究将会 活体皮内微渗析结合血流的应用 采用激光多普勒流量计进行测量。

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.