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, Maryland 20892.
Am J Cardiol. 1995 Feb 1;75(4):264-8. doi: 10.1016/0002-9149(95)80033-o.
Hormone replacement therapy is associated with a reduction in cardiovascular events in postmenopausal women. We have recently found that acute 17 beta-estradiol administration improves endothelium-dependent vasodilation in both the peripheral and coronary circulations of postmenopausal women. The current study was undertaken in 33 estrogen-deficient postmenopausal women (mean age 59 +/- 7 years) to determine if short-term estrogen replacement therapy also improves endothelium-dependent vasodilation in peripheral circulation. Acute intraarterial infusion of estradiol, which increased forearm venous estradiol levels from 16 +/- 11 to 345 +/- 202 pg/ml, potentiated forearm vasodilation induced by the endothelium-dependent vasodilator acetylcholine by 49 +/- 67% (p < 0.001). Acute estradiol also potentiated vasodilation induced by the endothelium-independent vasodilator nitroprusside by 5 +/- 31% (p = 0.04). However, after 3 weeks of transdermal estradiol administration (0.1 mg/day), which achieved an estradiol level of 120 +/- 57 pg/ml, the vasodilator responses to acetylcholine and to sodium nitroprusside were unchanged from initial measurements obtained before acute administration of estradiol. Repeat intraarterial infusion of estradiol in 8 women, while receiving transdermal estradiol, increased forearm venous estradiol levels to 268 +/- 105 pg/ml and again potentiated the vasodilator response to acetylcholine to a similar degree as that observed in the initial study after acute administration of estradiol. Thus, although acute intraarterial infusion of 17 beta-estradiol potentiates endothelium-dependent vasodilation in the forearms of postmenopausal women, this effect is not maintained with a 3-week cycle of systemic estradiol administration. The different effects of acute and chronic estradiol may be due to the lower plasma levels achieved with chronic estrogen administration.
激素替代疗法与绝经后女性心血管事件的减少有关。我们最近发现，急性给予17β-雌二醇可改善绝经后女性外周和冠状动脉循环中内皮依赖性血管舒张功能。本研究对33名雌激素缺乏的绝经后女性（平均年龄59±7岁）进行，以确定短期雌激素替代疗法是否也能改善外周循环中的内皮依赖性血管舒张功能。急性动脉内输注雌二醇使前臂静脉雌二醇水平从16±11 pg/ml升高至345±202 pg/ml，使内皮依赖性血管舒张剂乙酰胆碱诱导的前臂血管舒张增强49±67%（p<0.001）。急性雌二醇还使非内皮依赖性血管舒张剂硝普钠诱导的血管舒张增强5±31%（p = 0.04）。然而，在经皮给予雌二醇3周（0.1 mg/天）后，雌二醇水平达到120±57 pg/ml，此时对乙酰胆碱和硝普钠的血管舒张反应与急性给予雌二醇前的初始测量值相比没有变化。在8名接受经皮雌二醇治疗的女性中重复动脉内输注雌二醇，使前臂静脉雌二醇水平升高至268±105 pg/ml，并再次使对乙酰胆碱的血管舒张反应增强至与急性给予雌二醇后的初始研究中观察到的相似程度。因此，尽管急性动脉内输注17β-雌二醇可增强绝经后女性前臂的内皮依赖性血管舒张功能，但这种作用在系统性雌二醇给药3周的周期内并不能维持。急性和慢性雌二醇的不同作用可能是由于慢性雌激素给药所达到的较低血浆水平所致。
