Effects of nicorandil and its congeners on musculature and vasculature of the dog trachea in situ.

In anesthetized dogs, the tracheal vascular bed in situ was perfused with arterial blood through the cannulated cranial thyroid arteries. The effects of nicorandil, a coronary vasodilator, and its congeners (SG-212, GS-209 and SG-103; in which the nitroxy group of nicorandil was substituted for other groups) on the tracheal musculature and vasculature were examined. All drugs were injected intra-arterially. Nicorandil (10-300 micrograms), SG-212 (100 micrograms-3 mg), SG-209 (100 micrograms-3 mg) and SG-103 (100 micrograms-3 mg) all produced a decrease in tracheal tone elevated by neostigmine (tracheal dilatation) and an increase in tracheal blood flow (tracheal vasodilatation). Relative potencies of these effects were in the descending order: nicorandil greater than SG-212 = SG-209 = SG=103 in producing tracheal vasodilatation. These results suggest that nicorandil would also be a potential bronchodilator and that the nitrate site in nicorandil plays a role in potentiating the pharmacological activity of congeners of nicorandil.