SYSTEMIC VASCULAR EFFECTS OF 17 BETA-ESTRADIOL IN POSTMENOPAUSAL WOMEN

雌激素替代疗法与减少 绝经后妇女的心血管事件，尽管其机制 好处还不得而知。我们进行了研究，以确定急性和 雌激素对血管内皮细胞依赖性的慢性影响 绝经后雌激素缺乏妇女的血管扩张。三十三岁 绝经后妇女，年龄59岁加/减7岁(均数加/减SD) 参与了这项研究。雌激素对血管紧张素转换酶活性的影响 血管内皮依赖性扩张剂对前臂血管的反应 乙酰胆碱与非内皮依赖性血管扩张剂钠 硝普钠在5%急性动脉内输液中的研究 葡萄糖溶液和17β-雌二醇，经皮渗透3周后 17β-雌二醇组。急性动脉内输注17 β-雌二醇，它增加了前臂静脉雌二醇的水平 16加/减11至345加/减202 pg/ml，增强了前臂 乙酰胆碱引起的血管扩张几乎50%，而不是5% 葡萄糖对小鼠前臂血管扩张作用不明显。 硝普钠。然而，在雌二醇透皮吸收3周后 给药(每3天1毫克贴片)，达到雌二醇水平 120plus/-57pg/ml时，血管扩张剂对乙酰胆碱和 硝普钠与基线无明显变化。重复输液 8名女性在使用贴片时雌二醇水平升高 268加/减105 pg/ml，并再次增强血管扩张剂反应 对乙酰胆碱的影响程度与基线观察到的程度相似 学习。因此，我们得出结论，急性动脉内输注17 β-雌二醇增强大鼠血管内皮依赖性血管扩张 绝经后妇女的前臂。然而，这种影响并不是 维持长期(3周)全身服用雌二醇组。这个 急性和慢性雌激素的不同作用可能是由于较低的 达到的血浆水平，耐受性的发展，还是不同 慢性给药的细胞作用机制。

Estrogen replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, although the mechanism of benefit is unknown. We undertook studies to determine the acute and chronic effects of estrogen administration on endothelium-dependent vasodilation in estrogen-deficient postmenopausal women. Thirty-three postmenopausal women, aged 59plus/minus7 years (meanplus/minusSD) participated in this study. The effects of estrogen administration on the forearm vascular responses to the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside were studied during acute intra-arterial infusions of 5% dextrose solution and 17 beta-estradiol, and after 3 weeks of transdermal 17 beta-estradiol administration. Acute intra-arterial infusion of 17 beta-estradiol, which increased forearm venous estradiol levels from 16plus/minus11 to 345plus/minus202 pg/ml, potentiated the forearm vasodilation induced by acetylcholine by almost 50% compared to 5% dextrose but had minimal effect on the forearm vasodilation induced by sodium nitroprusside. However, after 3 weeks of transdermal estradiol administration (.1 mg patch every 3 days), achieving an estradiol level of 120plus/minus57 pg/ml, the vasodilator responses to acetylcholine and to sodium nitroprusside were unchanged from baseline. Repeat infusion of estradiol in 8 women, while on the patch, increased estradiol levels to 268plus/minus105 pg/ml and again potentiated the vasodilator response to acetylcholine to a similar degree to that observed in the baseline studies. Thus, we conclude that acute intra-arterial infusion of 17 beta-estradiol potentiates endothelium-dependent vasodilation in the forearms of postmenopausal women. However, this effect was not maintained with chronic (3 week), systemic estradiol administration. The different effects of acute and chronic estradiol may be due to the lower plasma levels achieved, the development of tolerance, or different cellular mechanisms of action with chronic administration.