乙炔雌二醇可急性减弱绝经后女性对乙酰胆碱的异常冠状动脉血管舒缩反应。

Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women.

作者信息

Reis S E, Gloth S T, Blumenthal R S, Resar J R, Zacur H A, Gerstenblith G, Brinker J A

机构信息

Department of Medicine, Johns Hopkins University, Baltimore, Md.

出版信息

Circulation. 1994 Jan;89(1):52-60. doi: 10.1161/01.cir.89.1.52.

DOI:10.1161/01.cir.89.1.52

PMID:8281693

Abstract

BACKGROUND

Estrogen administration in postmenopausal women is associated with a 50% reduction in the clinical manifestations of coronary artery disease. The mechanisms are not known, although one potential explanation is estrogen-induced modulation of coronary vasoreactivity. Acetylcholine is an endothelium-dependent vasodilator that may be used to assess coronary vasoreactivity and elicits coronary responses that parallel those found with common daily vasomotor stimuli. Therefore, we tested whether estrogen attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women.

METHODS AND RESULTS

Acetylcholine-induced changes in coronary flow, resistance, and cross-sectional area were determined before and 15 minutes after intravenous administration of ethinyl estradiol (EE, 35 micrograms) in 15 postmenopausal women. The influence of estrogen on basal coronary flow, resistance, and epicardial cross-sectional area was also assessed by measuring these parameters before and after EE or placebo administration in 33 women. Estrogen altered basal coronary vasomotor tone in 22 women as manifested by an EE-induced 23.3 +/- 4.5% (mean +/- SEM) increase (P < .01) in coronary flow, a 15.0 +/- 3.2% decrease (P < .01) in resistance, and a 20.0 +/- 6.5% increase (P = .02) in epicardial cross-sectional area. Placebo administration in 11 women did not change these parameters. Estrogen also attenuated abnormal coronary vasomotor responses to acetylcholine. Seven women who exhibited a paradoxical acetylcholine-induced decrease in coronary flow (-33.5 +/- 12.3%, P < .01) and increase in resistance (38.9 +/- 14.1%, P = .05) and seven who had an abnormal acetylcholine-induced decrease in epicardial cross-sectional area (-14.2 +/- 4.4%; P = .04) did not have acetylcholine-induced changes in these parameters after EE administration. Acetylcholine-induced flow, resistance, and cross-sectional area responses before and after EE were significantly different (P < .01, P = .02, and P = .02, respectively). Normal coronary responses to acetylcholine were not affected by EE administration.

CONCLUSIONS

EE attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. EE also decreases basal coronary vasomotor tone as manifested by increased coronary flow, decreased resistance, and increased epicardial cross-sectional area. These acute effects of estrogen on coronary vasoreactivity may explain, in part, the cardioprotective effects of estrogen in postmenopausal women.

摘要

背景

绝经后女性使用雌激素可使冠状动脉疾病的临床表现减少50%。其机制尚不清楚，不过一种可能的解释是雌激素诱导的冠状动脉血管反应性调节。乙酰胆碱是一种内皮依赖性血管舒张剂，可用于评估冠状动脉血管反应性，并引发与常见日常血管舒缩刺激相似的冠状动脉反应。因此，我们测试了雌激素是否能减轻绝经后女性对乙酰胆碱异常的冠状动脉血管舒缩反应。

方法与结果

在15名绝经后女性静脉注射乙炔雌二醇（EE，35微克）之前和之后15分钟，测定乙酰胆碱诱导的冠状动脉血流、阻力和横截面积的变化。通过在33名女性中测量EE或安慰剂给药前后的这些参数，还评估了雌激素对基础冠状动脉血流、阻力和心外膜横截面积的影响。雌激素改变了22名女性的基础冠状动脉血管舒缩张力，表现为EE诱导冠状动脉血流增加23.3±4.5%（平均值±标准误）（P<.01）、阻力降低15.0±3.2%（P<.01）以及心外膜横截面积增加20.0±6.5%（P=.02）。11名女性服用安慰剂后这些参数未改变。雌激素还减轻了对乙酰胆碱异常的冠状动脉血管舒缩反应。7名女性表现出乙酰胆碱诱导的冠状动脉血流矛盾性减少（-33.5±12.3%，P<.01）和阻力增加（38.9±14.1%，P=.05），7名女性表现出乙酰胆碱诱导的心外膜横截面积异常减少（-14.2±4.4%；P=.04），在服用EE后这些参数未出现乙酰胆碱诱导的变化。EE给药前后乙酰胆碱诱导的血流、阻力和横截面积反应有显著差异（分别为P<.01、P=.02和P=.02）。对乙酰胆碱正常的冠状动脉反应不受EE给药影响。