Estrogen and Sympathetically Mediated Vasoconstriction

描述（由申请人提供）：女性比男性更不容易受到 心血管疾病，直到他们达到更年期，当停止卵巢 激素的产生伴随着动脉粥样硬化风险的增加， 冠状动脉疾病和血管功能障碍。虽然有几种机制 雌激素可以提供血管保护的观点已经提出， 雌激素如何对血管系统发挥有益作用尚不清楚。 这项提案的主要目标是研究雌激素对 在收缩骨骼肌中交感神经血管收缩的调节。到 完成这一目标的补充实验将在有意识的 人和麻醉大鼠。在绝经前后的妇女中， 前臂肌肉氧合和肌肉交感神经活动将 在休息时下体负压（LBNP）期间测量， 将与有节奏的握力练习期间进行的LBNP进行比较。研究 当雌激素水平很高时， 浓度降低，以确定雌激素对 交感神经介导的血管收缩。在大鼠中， 交感神经刺激对股动脉血流和后肢肌肉的影响 氧合将在休息和收缩后肢检查， 卵巢切除和假手术大鼠。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 以确定其在介导雌激素的有益作用中的可能作用， 在肌肉收缩期间的外周血液动力学。

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.