Coronary arteriovenous difference in stable end-products of nitric oxide metabolism, nitrate and nitrite, was increased in ischemic canine hearts. In accordance with the reduction of coronary blood flow by 40, 67, 80 and 100%, the plasma nitrate+nitrite concentration increased from 3.2 +/- 0.6 to 8.7 +/- 1.3, 12.5 +/- 1.8, 15.9 +/- 2.7, and 20.2 +/- 2.3 microM, respectively. The plasma nitrate+nitrite concentrations were further elevated during reperfusion. Administration of NG-nitro-L-arginine methyl ester decreased the production of both nitrate+nitrite and coronary blood flow; the former was restored by the concomitant administration of L-arginine. These findings suggest that the increases in the nitric oxide production result from the action of nitric oxide synthase during myocardial ischemia and reperfusion, decreasing coronary vascular resistance and attenuating myocardial ischemia.