Endothelin (ET) is a potent vasoconstrictive 21-amino acid peptide hormone released from vascular endothelium The effects of ET-1 on coronary and systemic hemodynamics in comparison with Bay K 8644, a Ca2+ agonist, were studied in halothane-anesthetized dogs. The modification of ET-1 effects by nicardipine, a voltage-dependent Ca2+ antagonist, was also investigated. Single bolus ET-1 (100 ng/ kg) and Bay K 8644 (30 ug) were administered consecutively into left circumflex coronary artery during intracoronary infusion of either 0.9% saline (0.5 ml/kg/h, n=11) or nicardipine (1 ug/kg/min, n=10). Coronary and systemic hemodynamic parameters were measured just prior to (baseline), during saline or nicardipine infusion and 1, 5, 10, 20, 30, 45, and 60 min after ET-1 injection. Also electrocardiographic changes were observed continuously. The results are as follows: 1) Both ET-1 and Ray K 8644 produced a marked and immediate reduction in coronary blood flow and an increase in coronary vascular resistance. 2) ET-1 evoked coronary vasoconstrictions were long-lasting as compared with transient actions of Bay K 8644. 3) ET-1 reduced peak systolic intramyocardial pressure (IMP), mean aortic pressure (MAP), and cardiac index (CI), in contrast Bay K 8644 increased IMP without any changes in MAP and CL 4) Nicardipine (1 ug/kg/min, i.c) produced a significant increase (2-fold) in coronary blood flow and a reduction (46%) in coronary vascular resistance, whereas other hemodynamic parameters remained unchanged. 5) Nicardipine partially attenuated coronary vascular and systemic effects of ET-1, but it completely prevented those of Bay K 8644. 6) ET-1 (100 ng/kg, i.c.) produced a significant ST segment elevation in electrocardiogram in all cases of the saline group, but in none of the nicardipine group. These findings suggest that ET-1 is a potent and long-lasting coronary vasoconstrictor and that its vasoconstrictive effect is mediated in part by promoting Ca2+ influx through a voltage-dependant Ca2+ channel since nicardipine only partially attenuated ET-1 induced cardiovascular effects.