HETEROGENEITY IN THE VASORELAXING EFFECT OF NICORANDIL ON DOG EPICARDIAL CORONARY-ARTERIES - COMPARISON WITH OTHER NO DONORS

The relaxation responses to nicorandil, nitroglycerin (NTG), and croma kalim were compared in isolated dog large (>1.5 mm inside diameter) an d small (<0.3 mm inside diameter) epicardial coronary arteries. Nicora ndil and NTG produced more potent relaxing effects in large coronary a rteries. In contrast, cromakalim produced greater relaxation in small arteries. No significant differences were observed in the nitric oxide (NO)-induced response after treatment with superoxide dismutase. The responses to 8-bromo-cyclic guanosine monophosphate (cGMP), SIN-1, and atrial natriuretic peptide did not differ in arteries of different si zes. Treatment with L-cysteine had no significant effect on the relaxa tion responses to NTG in both large and small coronary arteries. Oxyhe moglobin and glibenclamide inhibited relaxation induced by nicorandil in large and small coronary arteries. Oxyhemoglobin had a greater supp ressive effect on the response to nicorandil in large coronary arterie s than in small coronary arteries. Methylene blue inhibited the respon se to nicorandil in large coronary arteries. These findings suggest th at nicorandil behaves predominantly as a nitrate in large epicardial c oronary arteries rather than small epicardial arteries and that this d ifference between large and small coronary arteries with regard to the nitrate action of nicorandil may be the result of a pathway in which nicorandil is converted to NO.