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 cromakalim were compared in isolated dog large (>1.5 mm inside diameter) and small (<0.3 mm inside diameter) epicardial coronary arteries. Nicorandil and NTG produced more potent relaxing effects in large coronary arteries. 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 sizes. Treatment with L-cysteine had no significant effect on the relaxation responses to NTG in both large and small coronary arteries. Oxyhemoglobin and glibenclamide inhibited relaxation induced by nicorandil in large and small coronary arteries. Oxyhemoglobin had a greater suppressive effect on the response to nicorandil in large coronary arteries than in small coronary arteries. Methylene blue inhibited the response to nicorandil in large coronary arteries. These findings suggest that nicorandil behaves predominantly as a nitrate in large epicardial coronary arteries rather than small epicardial arteries and that this difference 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.