NITRIC OXIDE BIOACTIVITY AND CORONARY VASCULAR EFFECTS OF 17-BETA ESTRADIOL

在生理浓度下，17 β-雌二醇 增强内皮依赖性血管舒张， 绝经后妇女，但通过一个未知的机制。评估 一氧化氮对雌二醇的血管效应的贡献， 我们测量了冠状动脉心外膜和微血管反应， 冠状动脉内乙酰胆碱（范围3-300 mcg/min，持续2 min）， 冠状动脉内注射雌二醇75 ng/min 15 min后， 雌激素缺乏的女性，其中16人有血管造影证据 动脉粥样硬化或动脉粥样硬化的危险因素。该测试 在抑制一氧化氮合成后重复， 冠状动脉内NG-单甲基-L-精氨酸（L-NMMA）64 μ mol/min，持续5分钟。冠状动脉血流来源于 定量心外膜冠状动脉内血流速度 多普勒导丝远端的动脉直径测量值。雌二醇 乙酰胆碱刺激血流从54+/-42%增加 (mean+/-标准差）高于雌二醇给药前的基线值 输注至100高于基线值63%（p=0.007），和 增强微血管扩张， 冠状动脉阻力降低（从32+/-20降至46+/-15% 基线值，p=0.007） 浓度为470+/-192 pg/mL。情绪也趋于减轻 乙酰胆碱引起心外膜收缩程度 冠状动脉直径较基线低8+/-11至3+/-11% 值（p=0.123）。然而，在L-NMMA输注过程中， 长时间增强乙酰胆碱对冠状动脉的作用 动力学（冠状动脉血流从42+/-40增加到39+/-46% 高于基线值，p=0.777;冠状动脉阻力从 比基线值低23+/-21至19+/-30%，p=0.553;心外膜 直径从基线值以下8+/-8至8+/-11%降低， p=0.764）。我们的结论是，雌二醇的影响，在生理 内皮依赖性冠状血管舒张剂浓度 绝经后妇女的反应性由以下因素介导： 提高一氧化氮的生物利用度。一氧化氮可能是 部分负责雌激素的心脏保护作用， 观察性研究表明，当长期给药时 绝经后的妇女。

At physiological concentrations, 17beta- estradiol enhances endothelium-dependent vasodilation when administered to postmenopausal women, but by an unknown mechanism. To assess the contribution of nitric oxide to the vascular effects of estradiol, we measured coronary epicardial and microvascular responses to intracoronary acetylcholine (range 3-300 mcg/min for 2 min) before and after intracoronary estradiol 75 ng/min for 15 min in 20 estrogen-deficient women, 16 of whom had angiographic evidence of atherosclerosis or risk factors for atherosclerosis. This testing was repeated following inhibition of nitric oxide synthesis with intracoronary NG- monomethyl-L-arginine (L-NMMA) 64 mumol/min for 5 minutes. Coronary flow was derived from intracoronary flow velocity in quantitative epicardial coronary artery diameter measurements distal to the Doppler wire. Estradiol increased acetylcholine-stimulated flow from 54+/-42% (mean+/-standard deviation)above baseline values prior to estradiol infusion to 10063% above baseline values (p=0.007), and potentiated microvascular dilatation as evidenced by greater decrease in coronary resistance (from 32+/-20 to 46+/-15% below baseline values, p=0.007) at a coronary sinus estradiol concentration of 470+/-192 pg/mL. Estradiol also tended to lessen the severity of acetylcholine-induced decrease in epicardial coronary artery diameter from 8+/-11 to 3+/-11% below baseline valuse (p=0.123). However, during L-NMMA infusion, estradiol no longer potentiated the effects of acetylcholine on coronary dynamics (coronary flow increased from 42+/-40 to 39+/-46% above baseline values, p=0.777; coronary resistance decreased from 23+/-21 to 19+/-30% below baseline values, p=0.553; epicardial diameter decreased from 8+/-8 to 8+/-11% below baseline values, p=0.764). We conclude that the effects of estradiol at physiological concentrations on endothelium-dependent coronary vasodilator responsiveness in postmenopausal women are mediated by enhanced bioavailability of nitric oxide. Nitric oxide may be responsible in part for the cardioprotective effects of estrogen, as suggested by observational studies, when chronically administered to postmenopausal women.