Endothelin: Potential Role in Hypertension and Vascular Hypertrophy

Abstract

Abstract The endothelins are a family of 21–amino acid peptides that are powerful vasoconstrictors. They may also induce vascular hypertrophy. These peptides may participate through these two mechanisms in the pathogenesis of the elevation of blood pressure and/or in the maintenance of hypertension in both experimental animal models and human essential hypertension. This review presents evidence both in favor and against the involvement of endothelins in hypertension. Plasma levels of endothelin-1 are either normal or slightly elevated in experimental and human essential hypertension. Responses of blood vessels to endothelin-1 may be normal or depressed in many models of experimental hypertension and also in essential hypertension in humans. It has recently been demonstrated that endothelin content and mRNA are increased in blood vessels of deoxycorticosterone acetate–salt hypertensive rats. When endothelin receptor antagonists are administered chronically, elevation of blood pressure and development of vascular hypertrophy are blunted in this experimental model of hypertension. In contrast, spontaneously hypertensive rats do not exhibit any increase in either endothelin-1 mRNA or immunoreactive endothelin in blood vessels and fail to respond with lowering of blood pressure to long-term treatment with endothelin receptor antagonists. Blood pressure development in young spontaneously hypertensive rats is also unaffected by long-term administration of endothelin antagonists. Molecular genetic studies appear to support a genetic role of components of the endothelin system in Dahl salt-sensitive rats. In human essential hypertension, there is some evidence of activation of the endothelin system despite depressed responses of small arteries to endothelin-1 and normal circulating levels of endothelin-1 in plasma. Thus, a role of endothelins in high blood pressure is possible. Further research is necessary to establish in a more definitive way whether endothelins are involved in the pathophysiology of human essential hypertension.