Abstract
The spasmolytic mechanisms of nicorandil, a novel antianginal drug, were investigated using 3, 4-diaminopyridine (3, 4-DAP)-induced phasic contractions of isolated canine coronary arteries in comparison with those-of cromakalim and pinacidil. Nicorandil (10-4 M), cromakalim (10-6 M) and pinacidil (10-5 M) suppressed the phasic contractions. Pretreatment with glibenclamide (10-6 M), a specific blocking agent of ATP-sensitive K+ channel, eliminated the suppression of phasic contractions by these drugs; glibenclamide completely eliminated the suppression by cromakalim, while the eliminations against nicorandil and pinacidil were incomplete. The recoveries of peak tensions were only 56.8 % and 76.1 % for nicorandil and pinacidil, respectively. Nicorandil and pinacidil may suppress the phasic contractions via K+ channel opening and additional mechanisms. Methylene blue (10-7 ?? 10-5 M) alone, a guanylate cyclase inhibitor, had no effect on the suppression of phasic contractions by nicorandil. In the presence of glibenclamide (10-6 M), however, the pretreatment with methylene blue significantly augmented the recovery of peak tension for nicorandil. These results indicate that K+ channel openers may suppress the phasic contractions induced by 3, 4-DAP via ATP-sensitive K+ channels, and that additionally, nicorandil may suppress the phasic contractility through guanylate cyclase stimulation, as a nitrate.
