Possible role of endothelin in endothelial regulation of vascular tone.

In vascular beds, a potent vasoconstrictor of endothelin-1 (ET-1) is produced by endothelial cells and released preferentially to the basal side of endothelial cells. It acts on endothelial cells and on the underlying smooth muscle cells, as a modulator of vascular tone, in an autocrine and paracine manner. ET-1 induces release of relaxing factors (nitric oxide and prostacycline) from endothelial cells. Whether relaxation or constriction is predominantly elicited by endogenous ET-1 may depend on the concentration of ET-1 in vascular beds, the density and mode of distribution of ET receptor subtypes on the endothelial and smooth muscle cells, the turnover of the receptors, and the existing conditions of each vascular beds. When ET-1 is overproduced by endothelial cells at pathological conditions, endogenous ET-1 acts as a vasoconstrictor. However, ET-1 may act as a vasodilator at physiologically low concentrations, depending on the existing condition.