Endothelial injury, vasoconstriction, and its prevention.

The endothelial cell is an important determinant of vascular tone, and performs this function by the elaboration of several factors that modulate the contractile state of the vascular smooth muscle cell. In response to physical and molecular factors in the vasculature, the endothelial cell maintains basal vascular tone by the elaboration of prostacyclin, endothelium-derived relaxing factor, and endothelium-derived hyperpolarizing factor, all of which reduce vascular smooth muscle tone. With progressive dysfunction of or injury to the endothelium, however, vascular smooth muscle tone increases in response to reduced production or availability of these endothelium-derived vasorelaxants and increased production of the vasoconstrictor substances, endothelin and endothelium-derived constricting factor(s). Common determinants of endothelial dysfunction that contribute substantially to the progress of vascular diseases include hypercholesterolemia, hypertension, tobacco use, and diabetes mellitus. Current approaches to the reversal or attenuation of the progression of vascular diseases in which the endothelium plays an important role focus on pharmacotherapeutic methods by which to restore normal endothelial function.