Endothelin in hypertension.

Abstract

The endothelins, 21-amino-acid peptides produced by the endothelium of blood vessels and many other tissues such as the kidney, brain, endocrine organs, etc., are potent vasoconstrictors, and are also endowed with mitogenic and cell hypertrophic properties. Endothelin may be involved in the pathogenesis of hypertension through vascular, renal, endocrine, and neural effects. Although many studies have been performed to test the hypothesis that these peptides have a pathophysiologic role in hypertension, it is only recently that evidence has been found of enhanced production of endothelin-1 in some models of hypertension, particularly in blood vessels in deoxycorticosterone acetate-salt hypertensive rats. Vascular responses to endothelin-1 have been shown to be normal or depressed in many models of experimental hypertension, and also in humans with essential hypertension. Elevation of blood pressure and development of vascular hypertrophy is blunted in deoxycorticosterone acetate-salt hypertensive rats treated chronically with endothelin receptor antagonists. Spontaneously hypertensive rats do not overexpress vascular endothelin, and do not exhibit a hypotensive response to chronic endothelin receptor antagonism. Malignant spontaneously hypertensive rats treated with deoxycorticosterone acetate and salt exhibit vascular overexpression of endothelin-1 and respond to endothelin antagonists with lowering of blood pressure. A genetic role of components of the endothelin system has been suggested in Dahl salt-sensitive rats. In human essential hypertension, there is as yet little evidence of activation of the endothelin system. A role of endothelins in hypertension is thus becoming increasingly apparent in severe forms of experimental hypertension, but further studies are required to establish whether these peptides are involved in the human disease.