[The vasospasmolytic effects of nicorandil, cromakalim and pinacidil on 3,4-diaminopyridine-induced phasic contractions in canine coronary arteries as an experimental vasospasm model].
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.
Kamijo
T
T
Second Department of Internal Medicine, University of Tokyo, Japan.
Tomaru
T
T
Miwa
A
A
Nakamura
F
F
Kido
H
H
Sugimoto
T
T
Uchida
Y
Y
D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D000077770:Amifampridine; D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003329:Coronary Vasospasm / Q000188:drug therapy*; D019806:Cromakalim; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D020108:Nicorandil; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D020110:Pinacidil; D015761:4-Aminopyridine; D000077770:Amifampridine; D005905:Glyburide; D008751:Methylene Blue