SYSTEMIC VASCULAR EFFECTS OF 17 BETA-ESTRADIOL IN POSTMENOPAUSAL WOMEN

17 β-雌二醇对绝经后女性的全身血管影响

• 批准号: 3757704
• 负责人: R O CANNON
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3757704
• 关键词: acetylcholine; endocrine pharmacology; estradiol; female; hormone therapy; human subject; human therapy evaluation; intraarterial administration; nitroferricyanide; postmenopause; vasodilation

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.

雌激素替代疗法与减少 绝经后妇女的心血管事件，尽管 好处是未知的。 我们进行了研究，以确定急性和 雌激素给药对内皮依赖性 雌激素缺乏的绝经后妇女的血管舒张。 三十三 绝经后女性，年龄59 ± 7岁（平均± SD） 参与了这项研究。 雌激素给药对 前臂血管对内皮依赖性血管舒张剂的反应 乙酰胆碱和内皮非依赖性血管舒张剂钠 硝普钠在急性动脉内输注5% 葡萄糖溶液和17 β-雌二醇，并在3周的透皮给药后， 17 β-雌二醇给药。 急性动脉内输注17 β-雌二醇，这增加了前臂静脉雌二醇水平， 16 +/-11至345 +/-202 pg/ml，增强前臂 乙酰胆碱诱导的血管舒张几乎50%，而5% 葡萄糖诱导的前臂血管舒张作用最小， 硝普钠 然而，经过3周的雌二醇透皮给药后， 给药（每3天0.1毫克贴片），达到雌二醇水平 在120 ± 57 pg/ml的浓度下，血管舒张剂对乙酰胆碱和 硝普钠与基线相比无变化。 重复输注 8名女性的雌二醇水平，而在贴片上， 至268 ± 105 pg/ml，再次增强血管舒张反应 与基线中观察到的相似程度 问题研究 因此，我们得出结论，急性动脉内输注17 β-雌二醇增强内皮依赖性血管舒张， 绝经后妇女的前臂。 然而，这种影响并没有 长期（3周）全身性雌二醇给药维持。 的 急性和慢性雌二醇的不同影响可能是由于较低的 达到的血浆水平，耐受性的发展，或不同的 长期给药的细胞作用机制。