Coronary artery disease remains a major cause of morbidity and mortality. Experimental and clinical data have indicated an important role of endothelin-1 at various subclinical and clinical stages of the disease. Endothelin-1 causes endothelial dysfunction and inflammation and may contribute to atherosclerotic plaque formation. During acute myocardial infarction, endothelin-1 enhances myocardial necrosis and arrhythmogenesis, but seems to exert a favorable effect on subsequent infarct healing and early ventricular remodeling. In the chronic postinfarction phase, endothelin-1 increases left ventricular afterload and participates in the myocardial fibrotic process. The progressive understanding of these actions has stimulated a large number of experimental and clinical studies examining the various effects of endothelin receptor blockade in coronary artery disease and chronic heart failure. However, this research has yielded largely contradictory results that have stirred scientific debates and controversies. This review summarizes the current state-of-the-art on this exciting topic, focusing on potential clinical ramifications.

Objective: Endothelin-1 (ET-1) production increases during acute myocardial infarction (MI) and may contribute to the genesis of ventricular tachycardia (VT) and ventricular fibrillation (VF). However, the antiarrhythmic effects of ET-1 receptor blockade, examined shortly after MI, have been debated. In the present study, we examined the effects of such treatment on VT/VF during the first 24 h post-MI. Methods: Thirty-five Wistar rats (223 ± 22 g) were randomly allocated to either the ET-1 receptor-A (ET_A) antagonist BQ-123 (0.4 mg/kg, BQ-123 group, n = 17), or normal saline (control group, n = 18) and were subjected to coronary artery ligation. A single-lead electrocardiogram was continuously recorded for 24 h post-MI, using an implanted telemetry system, and episodes of VT/VF were analyzed. Monophasic action potential (MAP) recordings were obtained from the left (LV) and right (RV) ventricular epicardium at baseline, 5 min after treatment and 24 h post-MI. Results: There were 15.94 ± 19.35 episodes/h/rat of VT/VF in the control group and 1.66 ± 2.22 in the BQ-123 group (p = 0.010), resulting in a lower (p = 0.030) arrhythmic mortality in treated animals. The mean episode duration was 7.40 ± 7.16 s for the control group and 2.30 ± 1.37 s for the BQ-123 group (p = 0.011). The maximum decrease in VT/VF was observed during the 1st, 5th and 6th hours post-MI. In the control group, LV MAP duration increased 24 h post-MI, displaying an increased beat-to-beat variation, but remained unchanged in the BQ-123 group. Conclusion: Acute ET_A blockade reduces the incidence of VT/V F during the first 24-h post-MI in the rat, through a decrease in the dispersion of repolarization.