Endothelin antagonists for hypertension: has their time finally arrived?

Abstract

There have been few new treatments introduced for hypertension in the last thirty years. The endothelin (ET) system was discovered in 1988, and in the following years, it was demonstrated that it participated in the elevation of blood pressure and vascular remodeling in experimental models of hypertension, particularly those with more severe forms of hypertension. Several selective and dual antagonists of ETA receptors (ETARs) and ETB receptors (ETBRs) were developed, but none reached marketing for human hypertension. Following a successful trial in resistant hypertension, a novel antihypertensive agent has been approved in Europe and in the U.S.A.: the dual ETAR/ETBR antagonist aprocitentan, which was recently approved for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. Thus, the time has finally arrived for ET antagonists in hypertension.