Gilligan D M, Badar D M, Panza J A, Quyyumi A A, Cannon R O
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Circulation. 1994 Aug;90(2):786-91. doi: 10.1161/01.cir.90.2.786.
Although hormone replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanisms that mediate this apparent benefit are unclear. Because improvement in vasomotor function may represent one of the beneficial effects of estrogen administration, we investigated the acute effects of physiological levels of estrogen on the vascular responses of estrogen-deficient postmenopausal women.
The study included 40 postmenopausal women 60 +/- 8 years old (mean +/- SD), 20 of whom had one or more conditions associated with vascular dysfunction (hypertension, hypercholesterolemia, diabetes, or coronary artery disease). The forearm vascular responses to the endothelium-dependent vasodilator acetylcholine were studied before and during infusion of 17 beta-estradiol into the ipsilateral brachial artery. In 31 subjects, the effect of estradiol on the responses to the endothelium-independent vasodilator sodium nitroprusside was also studied. Women with risk factors for vascular dysfunction had significantly reduced vasodilator responses to acetylcholine (P = .01) and to sodium nitroprusside (P < .001) compared with healthy subjects. Intra-arterial infusion of 17 beta-estradiol increased the forearm venous estradiol concentration from 16 +/- 10 to 318 +/- 188 pg/mL, levels typical of reproductive-age women at midcycle, but caused no vasodilation. However, estradiol potentiated the forearm vasodilation induced by acetylcholine by 18 +/- 30% (P < .001) in women with risk factors for vascular dysfunction and by 14 +/- 23% (P = .03) in healthy women. Estradiol also potentiated the forearm vasodilation induced by sodium nitroprusside in women with risk factors for vascular dysfunction by 14 +/- 21% (P < .001) but not in healthy women.
Physiological levels of 17 beta-estradiol selectively potentiate endothelium-dependent vasodilation in healthy postmenopausal women and potentiate both endothelium-dependent and endothelium-independent vasodilation in post-menopausal women with risk factors for atherosclerosis and evidence of impaired vascular function. These vascular effects may be partly responsible for the long-term benefit of estrogen therapy on cardiovascular events in postmenopausal women.
尽管激素替代疗法与绝经后女性心血管事件的减少有关，但介导这种明显益处的机制尚不清楚。由于血管舒缩功能的改善可能是雌激素给药的有益作用之一，我们研究了生理水平的雌激素对雌激素缺乏的绝经后女性血管反应的急性影响。
该研究纳入了40名60±8岁（平均±标准差）的绝经后女性，其中20名患有一种或多种与血管功能障碍相关的疾病（高血压、高胆固醇血症、糖尿病或冠状动脉疾病）。在向同侧肱动脉输注17β-雌二醇之前和期间，研究了前臂血管对内皮依赖性血管舒张剂乙酰胆碱的反应。在31名受试者中，还研究了雌二醇对内皮非依赖性血管舒张剂硝普钠反应的影响。与健康受试者相比，有血管功能障碍危险因素的女性对乙酰胆碱（P = 0.01）和硝普钠（P < 0.001）的血管舒张反应显著降低。动脉内输注17β-雌二醇使前臂静脉雌二醇浓度从16±10 pg/mL增加到318±188 pg/mL，这是育龄期女性月经周期中期的典型水平，但未引起血管舒张。然而，在有血管功能障碍危险因素的女性中，雌二醇使乙酰胆碱诱导的前臂血管舒张增强了18±30%（P < 0.001），在健康女性中增强了14±23%（P = 0.03）。雌二醇还使有血管功能障碍危险因素的女性中硝普钠诱导的前臂血管舒张增强了14±21%（P < 0.001），但在健康女性中未增强。
生理水平的17β-雌二醇选择性地增强健康绝经后女性的内皮依赖性血管舒张，并增强有动脉粥样硬化危险因素且有血管功能受损证据的绝经后女性的内皮依赖性和内皮非依赖性血管舒张。这些血管效应可能部分解释了雌激素治疗对绝经后女性心血管事件的长期益处。
