Neuropeptide-Y (NPY) was administered intracoronarily in dogs to see the modification of its vasoconstrictor action by the calcium (Ca)-channel blockers nisoldipine (0.1 microgram/kg) and nifedipine (1 microgram/kg). Dogs were anesthetized and the left circumflex artery was cannulated without opening the chest by using a specially designed cannula perfused at constant pressure. The change in coronary flow due to NPY was determined before and after the systemic administration of the two Ca-channel blockers. With administration of 1 to 2 nmol of NPY, coronary blood flow decreased maximally by 23.4 +/- 7.8% without changes in perfusion pressure or central venous pressure and it became significantly less after nisoldipine: 16.0 +/- 5.7% (p less than 0.02). A similar attenuation in the decrease in coronary flow was observed in the nifedipine study: 23.2 +/- 7.5% to 12.0 +/- 6.7% (p less than 0.02). A fall in systemic arterial blood pressure was observed after administration of both Ca-channel blockers, but it was significant only after nisoldipine (p less than 0.01). Nonsignificant increases in heart rate were observed after both drugs. Nisoldipine seemed to attenuate the NPY-induced vasoconstriction in dogs, and its equimolar potency is about ten times that of nifedipine.