Vascular effects of estrogens: rapid actions, novel mechanisms, and potential therapeutic implications.
Although estrogen-dependent effects on the vasculature were first observed more than a century ago, many of the mechanisms by which estrogens interact with the vascular wall have been identified only in the past 15 years. Estrogens bind to vascular estrogen receptors (ER), including the ER alpha, the novel ER beta as well as to membrane-bound receptors. Estrogens have direct effects in human coronary and internal mammary arteries by inducing rapid, endothelium-independent relaxation, enhancement of endothelial function and inhibition of vasoconstriction by vasoactive agonists. Furthermore, estrogens contribute to vascular homeostasis through modulation of gene expression, changes in membrane potentials, as well as expression and function of receptors. In addition, estrogens interfere with the activity of vasoactive peptides and vascular enzymes and act as natural antioxidants. Some of these effects have also been observed for phyto-estrogens, which are important dietary components in Asian countries. In the vasculature, the sum of these actions of estrogens results in vasodilatation and inhibition of vascular cell growth. Accordingly, estrogens have been shown to improve vascular function of animals and humans and to inhibit the response to injury after balloon angioplasty and the progression of atherosclerosis. Prospective clinical studies are ongoing to determine whether replacement therapy with estrogen or derivatives provides an alternative to lower cardiovascular mortality in postmenopausal women.
Barton
M
M
University Hospital Zürich, Switzerland. MatthiasBarton@compuserve.com
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III; D014664:Vasodilation / Q000187:drug effects*
D004967:Estrogens; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III