Cardiopulmonary indications for endothelin receptor antagonists: review of recent efficacy trials.
Recent clinical and experimental animal trials indicate that endogenously produced endothelin-1 (ET-1) contributes to the abnormal systemic and pulmonary vascular resistance associated with congestive heart failure (CHF) and pulmonary hypertension (PH). In experimental CHF, the chronic blockade of ET-1 actions by ET receptor antagonists clearly improves haemodynamic status, and improves cardiac structure and survival. The latter is based on limited results. In experimental PH there are consistent reports of prevention and reversal of PH, pulmonary vascular remodelling and right ventricular hypertrophy, independent of the inciting mechanisms. These results in experimental animals illustrate the potential efficacy of the ET receptor antagonists in future clinical trials. With five ET receptor antagonists in clinical development, and more on the way, their potential will soon be realised.
Department of Vascular and Cardiac Diseases, Parke-Davis Pharmaceutical Research Division, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. HALEENS@aa@WL.com
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Haleen
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Cheng