Estrogen and Sympathetically Mediated Vasoconstriction

描述(由申请者提供)：女性比男性更不容易患上 心血管疾病，直到绝经，当卵巢停止 荷尔蒙的产生伴随着动脉粥样硬化风险的加速， 冠状动脉疾病和血管功能障碍。尽管有几种机制 雌激素可能提供血管保护的机制已经被提出，但它仍然存在 不清楚雌激素如何对血管系统起到有益的作用。 这项建议的主要目标是检查雌激素对 骨骼肌收缩时交感血管收缩的调节。至 为了达到这个目标，补充实验将在有意识中进行。 人类和麻醉的大鼠。绝经前和绝经后妇女的变化 前臂肌肉氧合和肌肉交感神经活动将 下体负压(LBNP)静息时的测量及反应 将与在有节奏的握力练习中进行的下体负压进行比较。研究 将在雌激素水平较高时进行，当雌激素水平较高时再次进行 降低浓度以确定雌激素对 交感神经介导的血管收缩。在大鼠中，腰椎的作用 交感神经刺激对股动脉血流量和后肢肌肉的影响 氧合作用将在休息和收缩后肢中进行检查 卵巢切除组和假手术组大鼠。进一步的研究将考察 雌激素水平对骨骼肌神经元型一氧化氮合酶表达的影响 以确定其在调节雌激素对人体健康的有益作用中的可能作用。 肌肉收缩时的外周血流动力学。

DESCRIPTION (provided by applicant): Women are less susceptible than men to cardiovascular disease until they reach menopause, when cessation of ovarian hormone production is accompanied by an accelerated risk for atherosclerosis, coronary artery disease, and vascular dysfunction. Although several mechanisms by which estrogen may confer vascular protection have been proposed it remains unclear as to how estrogen exerts its beneficial effects on the vasculature. The main goal of this proposal is to examine the influence of estrogen on the regulation of sympathetic vasoconstriction in contracting skeletal muscle. To accomplish this goal complementary experiments will be performed in conscious humans and anesthetized rats. In pre and post-menopausal women changes in forearm muscle oxygenation and muscle sympathetic nerve activity will be measured during lower body negative pressure (LBNP) at rest and the responses will be compared to LBNP performed during rhythmic handgrip exercise. Studies will be performed when estrogen levels are high and again when estrogen concentrations are reduced to determine the impact of estrogen on sympathetically mediated vasoconstriction. In rats, the effect of lumbar sympathetic nerve stimulation on femoral blood flow and hind limb muscle oxygenation will be examined in resting and contracting hind limb of ovariectomized and sham rats. Further studies will examine influences of estrogen levels on neuronal nitric oxide synthase expression in skeletal muscle to determine its possible role in mediating a beneficial effect of estrogen on peripheral hemodynamics during muscle contraction.