McLemore G L, Billingsley M L, Severs W B
Department of Pharmacology, College of Medicine, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033.
Pharmacology. 1993 Aug;47(2):126-34. doi: 10.1159/000139087.
Potential alteration of ouabain-induced cardiotoxicity by gamma-aminobutyric acid (GABA) in rats was tested by infusing ouabain for 10 min (0.7 mg/kg/min, i.v.) before or after continuous infusion of Ringer's solution with or without GABA (1 mg/min, i.v.). GABA evoked hypotension and bradycardia of similar magnitude under both conditions. The incidence of ouabain-induced ventricular fibrillation (VF) or cardiac arrest (CA) was similar in both groups. However, the time intervals to onset of VF and CA, in rats given ouabain before, but not after, GABA were shorter than in rats treated with Ringer's solution (p < 0.05). In experiments where baclofen (0.034 mg/min, i.v.) was infused after ouabain, hypotension and bradycardia occurred, but the incidence and times of ouabain-induced VF and CA were similar to control values. These results suggest that the enhancement in ouabain cardiotoxicity was mediated by GABAA receptors.
通过在静脉输注含有或不含有γ-氨基丁酸(GABA,1毫克/分钟)的林格氏液之前或之后静脉输注哇巴因10分钟(0.7毫克/千克/分钟),来测试GABA对大鼠哇巴因诱导的心脏毒性的潜在改变。在两种情况下,GABA引起的低血压和心动过缓程度相似。两组中哇巴因诱导的心室颤动(VF)或心脏骤停(CA)的发生率相似。然而,在给予GABA之前而非之后给予哇巴因的大鼠中,VF和CA发作的时间间隔比用林格氏液治疗的大鼠短(p<0.05)。在哇巴因后静脉输注巴氯芬(0.034毫克/分钟)的实验中,出现了低血压和心动过缓,但哇巴因诱导的VF和CA的发生率及时间与对照值相似。这些结果表明,哇巴因心脏毒性的增强是由GABAA受体介导的。