It is generally accepted that endothelin-1 (ET-1) may contribute to the pathogenesis of a number of cardiovascular diseases. Although still controversial, ET-1 may also be involved in blood pressure regulation as well as functional and structural changes in arterial hypertension. Beneficial effects of ET-1 antagonism in experimental models of hypertension have set the stage for the clinical use of ET-1–receptor antagonists. However, it is still a matter of debate whether selective ETA or nonselective ETA/ETBreceptor antagonists provide the best approach to blocking the effects of ET-1 in man. Future head-tohead comparative, large-scale studies with these pharmacological agents will provide us with further insight into the pathophysiological role of ET-1 and eventually prove whether they represent a therapeutic advance in the treatment of our patients...