Help
The vascular endothelium plays a crucial role in the regulation of vascular homeostasis by controlling vascular tone, coagulation, and inflammatory responses. These actions are exerted by endothelial factors including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The greater incidence of cardiovascular disease (CVD) in men and postmenopausal women compared with premenopausal women implies a vasoprotective phenotype of females, which may be influenced by sex hormones. These hormones, particularly estrogen, have modulatory effects on the endothelium and circulating cells that have been implicated in vascular inflammation and in the development of CVD. EDHF seems to be the predominant endothelial factor in the resistance vasculature of females and this mediator could afford the beneficial cardiovascular risk profile observed in premenopausal woman. In this review, we discuss sex differences in EDHF biology and how sex hormones can modulate EDHF responses. We also review the implication of sex hormone-dependent regulation of EDHF in inflam- matory processes, platelet function, and repair after vascular damage, each of which have a critical role in several aspects of the pathogenesis of CVD.
Endothelium-derived factors not only alter the tone and growth of the underlying smooth muscle, but also regulate the reactivity of circulating white cells, erythrocytes, and platelets and govern vascular permeability. Indeed, the endothelium is critical in maintaining an anti-inflammatory, and thereby anti- atherogenic, influence on the blood vessel wall. In the early stages of several inflammatory CVDs, a switch in endothelial phenotype occurs from a protective anti-inflammatory to a pro-inflammatory phenotype, characterized by the production of pro-inflammatory mediators. Much evidence supports the thesis that estrogens upregulate the synthesis, release, and activity of protective endothelial factors and suppress the expression of pathogenic mediators by the endothelium and, thereby, preventing this apparent change in phenotype.