Previous studies indicate impairment of coronary arterial ring relaxation in response to acetykholine (ACh) following coronary reperfusion, mediated via loss of endothetium-derived relaxing factor (EDRF). To examine if coronary vasodilator reserve is reduced following coronary ocdusfon-reperfusion in intact animnk, 16 open-chest mongrel dogs were subjected to 1 hour of total left circumflex (Cx) coronary artery occlusion followed by reperfusion for 1 hour. Prior to Cx occlusion, coronary blood flow increased and vascular resistance decreased (both p±O.Ol) in response to ACh and bradykinin (BK). Following reperfusion, Increase in Cx coronary flow in response to both vasodilators was significantly (p±O.Ol) impaired. Myocardial histology showed extensive neutrophil infiltration and capillary plugging by neutrophils in the Cx compared with the left anterior descending coronary artery-supplied myocardium. Myocardial myetoperoxidase activity was also increased in the Cx compared with the left anterior descending region (p±0.02). Pretreatment of four dogs with indomethadn partially reduced the vasodilator response to BK but not to ACh. However, indomethadn did not affect reperfusion-induced attenuation of BK or ACh's coronary vasodilator effects. To determine if calcium blocker verapamil would modify reperfusion-induced impairment in coronary vasodilator reserve, six dogs were treated with verapamil. Although verapamil enhanced coronary vasodilator effects of ACh and BK, it did not modify reperfusion-induced attenuation of coronary vasodilator reserve. Myocardial neutrophil accumulation and myeloperoxidase activity was also similar in control, indomethacin, and verapamil-treated dogs. These observations suggest that coronary reperfusion impairs coronary vasodilator reserve in intact dogs. This impairment is not modified by prostaglandin inhibition or by calcium blockade. Besides loss of EDRF, capillary plugging by neutrophils may contribute to the altered coronary flow reserve observed in the immediate post-reperfusfon period. Furthermore, indomethacin or verapamil are not effective in modifying the reperfusion-related impairment of coronary vasodilator reserve.