Endothelin in Hypertension: A Role in Vascular Hypertrophy?

Abstract

The endothelins are 21-amino acid peptides with potent vasoconstrictor effects. These peptides have as well mild mitogenic and cell hypertrophic effects. Endothelin-1 is the main endothelin produced by the endothelium. Plasma levels of immunoreactive endothelin are normal or only slightly increased in experimental or human hypertension. The responsiveness of blood vessels to endothelin-1 is normal or attenuated in experimental and human hypertension. Endothelin-1 expression is increased in the endothelium of blood vessels in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat and DOCA-salt treated spontaneously hypertensive rats (SHR), in association with exaggerated vascular hypertrophy in comparison to other models of hypertension. Endothelin receptor antagonist treatment attenuates partially the elevation of blood pressure and blunts to an important degree the development of vascular hypertrophy in these experimental models of hypertension, whereas it has no effect on SHR. The latter do not overexpress endothelin in blood vessels. In some severe hypertensive patients there is overexpression of endothelin-1 in endothelium of small arteries. These results suggest that endothelins may play a role in some experimental models of high blood pressure and perhaps in severe human hypertension, in part by accentuating hypertension-induced vascular hypertrophy.