Estrogen and vascular function.

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.