The role of nitric oxide in digoxin-induced arrhythmias in guinea-pigs

We have investigated the effects of nitric oxide synthase inhibitor (L-NAME ), nitric oxide precursor (L-arginine) and nitric oxide donor (sodium nitro prusside) on digoxin-induced arrhythmias both in guinea-pig isolated hearts and in anaesthetised animals. Sodium nitroprusside (0.1 mu mol kg(-l) min. (-1) for 70 min.) caused a marked inhibition in mortality and arrhythmia sc ore but L-NAME (10 mg kg(-1))and L-arginine (30 mg kg(-1) intravenous bolus followed by 10 mg kg(-1) min.(-1) for 60 min.) treatments were ineffective in anaesthetised guinea-pigs. None of the drugs markedly affected the time of onset of first arrhythmias or ventricular fibrillation incidence. In is olated heart experiments, nitric oxide generated by either L-arginine (1 mM ) or sodium nitroprusside (1 mM) significantly reduced the arrhythmia score whereas L-NAME (1 mM) had no effect. Ventricular fibrillation incidence wa s totally abolished by sodium nitroprusside and none of the hearts treated with L-arginine had an irreversible ventricular fibrillation. L-NAME decrea sed ventricular tachycardia duration but increased ventricular fibrillation duration. There were no marked changes in the time of onset of first arrhy thmias with these drugs in in vitro experiments. These results suggest that nitric oxide may play a modulatory role in the digoxin-induced arrhythmias in guinea-pigs.