Altuğ S, Uzun O, Demiryürek A T, Cakici I, Abacioğlu N, Kanzik I
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
Pharmacol Toxicol. 1999 Jan;84(1):3-8. doi: 10.1111/j.1600-0773.1999.tb02103.x.
We have investigated the effects of nitric oxide synthase inhibitor (L-NAME), nitric oxide precursor (L-arginine) and nitric oxide donor (sodium nitroprusside) on digoxin-induced arrhythmias both in guinea-pig isolated hearts and in anaesthetised animals. Sodium nitroprusside (0.1 mumol kg-1 min.-1 for 70 min.) caused a marked inhibition in mortality and arrhythmia score 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 isolated 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 was totally abolished by sodium nitroprusside and none of the hearts treated with L-arginine had an irreversible ventricular fibrillation. L-NAME decreased ventricular tachycardia duration but increased ventricular fibrillation duration. There were no marked changes in the time of onset of first arrhythmias 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.
我们已经研究了一氧化氮合酶抑制剂（L-硝基精氨酸甲酯）、一氧化氮前体（L-精氨酸）和一氧化氮供体（硝普钠）对豚鼠离体心脏和麻醉动物中地高辛诱导的心律失常的影响。硝普钠（0.1 μmol·kg⁻¹·min⁻¹，持续70分钟）可显著降低死亡率和心律失常评分，但L-硝基精氨酸甲酯（10 mg·kg⁻¹）和L-精氨酸（静脉推注30 mg·kg⁻¹，随后以10 mg·kg⁻¹·min⁻¹持续60分钟）治疗对麻醉的豚鼠无效。这些药物均未显著影响首次心律失常的发作时间或室颤发生率。在离体心脏实验中，L-精氨酸（1 mM）或硝普钠（1 mM）产生的一氧化氮可显著降低心律失常评分，而L-硝基精氨酸甲酯（1 mM）则无作用。硝普钠完全消除了室颤发生率，用L-精氨酸治疗的心脏均未发生不可逆的室颤。L-硝基精氨酸甲酯缩短了室性心动过速的持续时间，但延长了室颤的持续时间。在体外实验中，这些药物对首次心律失常的发作时间没有明显影响。这些结果表明，一氧化氮可能在豚鼠地高辛诱导的心律失常中起调节作用。
