Gilligan D M, Quyyumi A A, Cannon R O
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Circulation. 1994 Jun;89(6):2545-51. doi: 10.1161/01.cir.89.6.2545.
Estrogen replacement therapy has been associated with a reduction in cardiovascular events in postmenopausal women. One of the mechanisms responsible may be a beneficial effect of estrogen on coronary vascular function. We therefore studied the short-term effects of estrogen on coronary artery dimensions and microvascular resistance in postmenopausal women.
Twenty postmenopausal women 61 +/- 7 years old participated in this study. Seven had angiographic evidence of atherosclerosis of the left coronary artery. Coronary artery diameters were measured by quantitative coronary angiography. Blood flow velocity was measured with a Doppler wire placed in a proximal left coronary artery segment. Left coronary artery infusions of acetylcholine (range, 10(-8) to 10(-5) mol/L estimated delivered concentrations) and of adenosine (n = 18) and sodium nitroprusside (n = 10) were performed before and during concomitant continuous intracoronary infusion of 17 beta-estradiol to test endothelium-dependent and independent vasodilation, respectively. Intracoronary infusion of estradiol increased coronary sinus estradiol levels from postmenopausal (16 +/- 11 pg/mL) to premenopausal (282 +/- 121 pg/mL) levels. Estradiol did not affect basal coronary artery diameter, blood flow, or resistance. Epicardial coronary artery constriction induced by acetylcholine infusion in the control study (maximum, 10 +/- 15% from baseline) was prevented during repeat acetylcholine infusion with concomitant estradiol administration (P < .001). Estradiol potentiated the vasodilator coronary microvascular response to acetylcholine as manifest by significantly greater coronary flow (P < .001) and lower coronary resistance (P < .02). The reduction in coronary resistance from baseline in response to acetylcholine was significantly potentiated by estradiol (P = .01), with a mean decrease in coronary vascular resistance during acetylcholine infusion of 20 +/- 38% before and 35 +/- 33% during concomitant estradiol administration. The effect of estradiol on coronary dynamics was similar in women with and women without angiographically apparent left coronary artery atherosclerosis and was most prominent in women with the most impaired responses to acetylcholine at both the epicardial (r = -.72, P < .001) and microvascular (r = -.59, P = .006) coronary artery levels. In contrast, estradiol did not affect the coronary epicardial or microvascular vasodilator responses to adenosine or sodium nitroprusside.
Physiological levels of 17 beta-estradiol acutely and selectively potentiate endothelium-dependent vasodilation in both large coronary conductance arteries and coronary microvasuclar resistance arteries of postmenopausal women. This effect may contribute to the reduction in cardiovascular events observed with estrogen replacement therapy.
雌激素替代疗法与绝经后女性心血管事件减少有关。其中一个可能的机制是雌激素对冠状动脉血管功能具有有益作用。因此，我们研究了雌激素对绝经后女性冠状动脉内径和微血管阻力的短期影响。
20名年龄在61±7岁的绝经后女性参与了本研究。其中7名有左冠状动脉粥样硬化的血管造影证据。通过定量冠状动脉造影测量冠状动脉直径。用置于左冠状动脉近端节段的多普勒导丝测量血流速度。在持续冠状动脉内输注17β - 雌二醇的同时，分别在输注乙酰胆碱（浓度范围为10⁻⁸至10⁻⁵mol/L估计递送浓度）、腺苷（n = 18）和硝普钠（n = 10）之前及期间进行左冠状动脉内输注，以分别测试内皮依赖性和非内皮依赖性血管舒张。冠状动脉内输注雌二醇使冠状窦雌二醇水平从绝经后（16±11 pg/mL）升高至绝经前（282±121 pg/mL）水平。雌二醇不影响基础冠状动脉直径、血流或阻力。在对照研究中，输注乙酰胆碱引起的心外膜冠状动脉收缩（最大为基线的10±15%）在重复输注乙酰胆碱并同时给予雌二醇时被预防（P < 0.001）。雌二醇增强了冠状动脉微血管对乙酰胆碱的血管舒张反应，表现为冠状动脉血流显著增加（P < 0.001）和冠状动脉阻力降低（P < 0.02）。雌二醇显著增强了乙酰胆碱引起的冠状动脉阻力相对于基线的降低（P = 0.01），在输注乙酰胆碱期间，冠状动脉血管阻力的平均降低在给予雌二醇之前为20±38%，同时给予雌二醇期间为35±33%。在有和没有血管造影显示左冠状动脉粥样硬化的女性中，雌二醇对冠状动脉动力学的影响相似，并且在对乙酰胆碱反应受损最严重的女性中最为显著，无论是在心外膜（r = -0.72，P < 0.001）还是微血管（r = -0.59，P = 0.006）冠状动脉水平。相比之下，雌二醇不影响冠状动脉心外膜或微血管对腺苷或硝普钠的血管舒张反应。
生理水平的17β - 雌二醇可急性且选择性地增强绝经后女性大冠状动脉传导血管和冠状动脉微血管阻力血管的内皮依赖性血管舒张。这种作用可能有助于解释雌激素替代疗法中观察到的心血管事件减少现象。
