Pro-arrhythmic effect of nicorandil in isolated rabbit atria and its suppression by tolbutamide and quinidine.
Nicorandil, a potent vasodilator substance which exerts its effects through complex mechanisms including KATP channel activation, has so far been reported to exert antiarrhythmic but not pro-arrhythmic cardiac activity. We now examined the effects of 10(-4) M nicorandil on spontaneously active or electrically driven isolated rabbit atria. Nicorandil (a) significantly reduced the action potential duration at both 50% (by approximately 45%) and 80% (by approximately 30%) repolarization and the effective refractory period (by approximately 25%) and (b) reproducibly induced short periods of tachycardia either in normal Tyrode solution after a single extra-stimulus or in low-potassium media in the absence of extra-stimulation. Quinidine (10(-5) M) or the KATP channel inhibitor, tolbutamide (10(-5) M), suppressed the nicorandil-induced arrhythmias. It is suggested that the pro-arrhythmic effect of nicorandil results from its KATP channel opener activity and occurs essentially when the underlying conditions facilitate re-entry.
Le Grand
B
B
Instrumentation et Dynamique Cardiovasculaire, INSERM (U256), Hôpital Broussais, Paris, France.
Hatem
S
S
Le Heuzey
J Y
JY
Deroubaix
E
E
Benitah
J P
JP
Coraboeuf
E
E
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D020108:Nicorandil; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011802:Quinidine / Q000494:pharmacology*; D011817:Rabbits; D013610:Tachycardia / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D014044:Tolbutamide / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*
D015221:Potassium Channels; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D014044:Tolbutamide; D011802:Quinidine