Ouabain cardiotoxicity is enhanced by GABA in anesthetized rats.
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.
McLemore
G L
GL
Department of Pharmacology, College of Medicine, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033.
Billingsley
M L
ML
Severs
W B
WB
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D006321:Heart / Q000187:drug effects*; D006323:Heart Arrest / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014693:Ventricular Fibrillation / Q000139:chemically induced; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D005680:gamma-Aminobutyric Acid; D010042:Ouabain