Studies on the protective effect of azepexole on ouabain-induced cardiac arrhythmias and lethality in guinea-pig

Abstract

Azepexole, an alpha 2-adrenoceptor agonist (125, 250 and 500 micrograms/kg i.v.), was examined for its effect on ouabain-induced ventricular premature beats, ventricular tachyarrhythmias and lethality in guinea-pigs. The doses of ouabain required to cause ventricular arrhythmias and lethality were significantly higher in azepexole-treated animals. However, it did not offer any protection in reserpinised guinea-pigs. Idazoxan, the alpha 2-adrenoceptor antagonist (100 micrograms/kg i.v.) inhibited the protective action of azepexole while corynanthine, the alpha 1-adrenoceptor antagonist (1 mg/kg i.v.), potentiated the effect. Azepexole inhibited the rate of the ouabain-induced rise in mean arterial blood pressure and the peak pressor response. In isolated paced left atria of guinea-pig, azepexole (2.76 x 10(-3) M) did not offer any protection against extrasystolic contractions induced by ouabain. Therefore the protective effect of azepexole may be mediated through the stimulation of alpha 2-adrenoceptors and the resultant suppression of the indirect neural components of ouabain toxicity.