[Therapeutic implications of endothelin antagonists for cardiovascular diseases]

The endothelin system plays an important role in the pathophysiology of a variety of cardiovascular diseases including: congestive heart failure, essential and pulmonary hypertension, renal failure, and cerebrovascular disease. The biological effects of endothelin-1 on its target organs are mediated by two receptors: ETA and ETB. It is widely accepted that the vascular, cardiac, and renal adverse effects of ET-1 are mediated by ETA, while activation of ETB receptors leads to beneficial effects such as: attenuating the vascular and cardiac hypertrophic effects of ET-1 as well as the vasodilatory action of this peptide. In the last decade, a whole range of peptide and non-peptide ET-1 antagonists has been developed, some selective to ETA and others nonselective with dual antagonistic activity against both ETA and ETB. Several clinical studies have revealed that ET-1 antagonists are clinically beneficial therapeutic agents for the treatment of several cardiovascular diseases, leading to the approval of bosentan (ETA/ETB antagonist) for the treatment of pulmonary hypertension. The current review will focus on the recent developments in the endothelin field, with special emphasis on the ET-1 antagonist and their clinical use.