The antiarrhythmic effect of (-)-U-50,488 in rats with acute ischemia and reperfusion of heart is mediated by kappa1-opioid receptor activation

摘要

Pretreatment with a selective kappa1 opioid receptor (OR) agonist (-)-U-50,488 (1 mg/kg, i.v.) prevented the development of arrhythmias induced by occlusion (10 min) and reperfusion (10 min) in ketamine anesthetized rats, while the treatment with a less active enantiomer (+)-U-50,488 in the same dose produced no such effects. Preliminary intravenous administration of a selective kappa1 OR antagonist norbinaltorphimine (9 mg/kg) fully abolished the antiarrhythmic effect of (-)-U-50,488, while the kappa2 OR antagonist quadazocine (3 mg/kg) did not eliminate this effect. The injections of norbinaltorphimine or quadazocine alone did not influence the incidence of model arrhythmias caused by the occlusion and reperfusion. It was concluded that kappa1 OR stimulation favors an increase in cardiac tolerance to the arrhythmogenic action of occlusion and reperfusion.