White Richard E
Department of Pharmacology and Toxicology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-2300, USA.
Vascul Pharmacol. 2002 Feb;38(2):73-80. doi: 10.1016/s0306-3623(02)00129-5.
The effects of estrogen on the female reproductive system are well known. In contrast, comparatively recent research has demonstrated that estrogen also exerts specific effects on the cardiovascular system--particularly the vasculature. This review summarizes some of the current ideas of how estrogen regulates and modulates vascular function, and focuses primarily on potential mechanisms of estrogen-induced vasodilation. Although many studies indicate estrogen exerts beneficial effects on the circulatory system, the overall conclusions from clinical studies remain somewhat equivocal. In contrast, it is clear that estrogen reduces atherosclerosis by reducing low-density lipoproteins (LDL) and inflammatory processes in the vasculature, and may also act as an antioxidant; however, these effects account for only a portion of the total cardiovascular benefit of estrogen. Estrogen is also a vasodilator and hypotensive agent, and can induce vascular relaxation by stimulating release of endothelium-derived vasodilatory substances (e.g., nitric oxide [NO]) or by acting directly on the vascular smooth muscle (VSM). Recent evidence indicates that calcium and potassium channels in VSM cells play an important role in mediating estrogen-induced relaxation of many vascular beds, but elucidating the signal transduction mechanisms coupling estrogen receptor (ER alpha and/or ER beta) activation to generation of second messengers and effector mechanisms remains an area of intense study. Not surprisingly, it is becoming apparent that the molecular basis of estrogen's influence on vascular function is multifactorial. A better understanding of these signaling mechanisms should lead to the development of powerful therapeutic agents which can maximize the many beneficial effects of estrogen action, while helping minimize the harmful (and sometimes lethal) side effects.
雌激素对女性生殖系统的作用众所周知。相比之下，近期研究表明雌激素对心血管系统，尤其是血管系统也有特定作用。本文综述了目前关于雌激素如何调节和调控血管功能的一些观点，主要聚焦于雌激素诱导血管舒张的潜在机制。尽管许多研究表明雌激素对循环系统有有益作用，但临床研究的总体结论仍有些模棱两可。相比之下，很明显雌激素通过降低低密度脂蛋白（LDL）和血管中的炎症过程来减轻动脉粥样硬化，并且可能还具有抗氧化作用；然而，这些作用仅占雌激素对心血管系统总益处的一部分。雌激素还是一种血管舒张剂和降压剂，可通过刺激内皮源性血管舒张物质（如一氧化氮[NO]）的释放或直接作用于血管平滑肌（VSM）来诱导血管舒张。最近的证据表明，VSM细胞中的钙通道和钾通道在介导雌激素诱导的许多血管床舒张中起重要作用，但阐明将雌激素受体（ERα和/或ERβ）激活与第二信使生成及效应器机制偶联的信号转导机制仍是一个深入研究的领域。毫不奇怪，雌激素对血管功能影响的分子基础显然是多因素的。更好地理解这些信号机制应能开发出强大的治疗药物，既能最大化雌激素作用的诸多有益效果，又有助于将有害（有时甚至是致命的）副作用降至最低。
