We assess hemodynamic, vascular, and hormonal effects of endothelin-1 (ET-1) at pathophysiologic levels on normal and ischemic myocardium. Thirty conscious chronically instrumented dogs were studied before, during, and after a 10-min coronary artery occlusion (CAO) performed either during ET-1 infusion (2.5 ng/kg.min, n = 15) or during placebo infusion (n = 15). ET-1 infusion produced an increase in plasma ET-1 (from 1.3 +/- 0.1 to 11.5 +/- 1.1 pM, p < 0.0001) during CAO (pathophysiologic value). Left anterior descending artery (LAD) blood flow (measured by Doppler flow probe) decreased similarly during CAO with ET-1 or placebo (p = 0.0001, NS, ET-1 vs. placebo). Both endocardial and epicardial blood flows in ischemic regions also decreased (p = 0.0001) during CAO but were threefold greater with ET-1 than with placebo (endocardium 42 +/- 7 vs. 14 +/- 2 ml/min/100 g, p = 0.003). No significant difference in myocardial blood flows between groups was observed in control regions. CAO produced increases (p < 0.005) in heart rate (HR), mean aortic pressure (AOP), and ventricular pressures but no change in atrial pressures. The changes in these parameters were comparable in the ET-1 and placebo groups. Despite the greater residual flow during CAO, however, ET-1 decreased the function of the ischemic zone during reperfusion as assessed by systolic shortening (p < 0.05). Atrial natriuretic factor (ANF), unchanged during CAO with placebo, increased from 38.3 +/- 6.1 to 53.3 +/- 10 pM with ET-1 (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)