Comparative Vasorelaxing Profiles of Nicorandil, Isosorbide Dinitrate and Nitroglycerin in Isolated Coronary Arteries of the Dog

The vasorelaxing effects of nicorandil (NCR), isosorbide dinitrate (ISDN) and nitroglycerin (NTG) were studied in isolated canine coronary arteries. In rings of coronary arteries precontracted with prostaglandin F2α (3×10-6 M) or KCI (30 mM), removal of the endothelium significantly augmented the relaxing effects of NCR, while it did not affect those of ISDN and NTG. In unrubbed rings precontracted with KCI (30 mM), methylene blue (5×10-6 M) significantly inhibited vasorelaxing responses to the three drugs. The order of the inhibition was as follows: NTG>ISDN>NCR. When the unrubbed tissue was incubated with NTG (10-5 M) or ISDN (10-4 M) for 10 min, it developed acute tolerance in relaxing response to NTG or ISDN. Unlike NTG and ISDN, NCR did not develop any tolerance. The treatment with N-acetylcysteine (5×10-5 M) tended to potentiate relaxant effects of NTG and to reduce the degree of acute tolerance to NTG. The results suggest that cGMP plays a role in the relaxation of the coronary artery induced by the drugs and furthermore that the mode of the vasorelaxing action of NCR may be somewhat different from that of NTG or ISDN.