Effect of in vivo and in vitro stimulation of delta1-opioid receptors on myocardial resistance to arrhythmogenic action of ischemia and reperfusion.

Preliminary intravenous injection of peptide agonist of delta1-opioid receptors DPDPE (0.5 mg/kg) decreased the incidence of occlusion (10 min) and reperfusion (10 min) arrhythmias in rats. By contrast, delta2-opioid receptor agonist DSLET produced no effect on the incidence of arrhythmias provoked by coronary occlusion and reperfusion. Preliminary injection of selective delta-receptor antagonist ICI 174,864 (2.5 mg/kg) or TIPP[y] (0.5 mg/kg) completely abolished the antiarrhythmic effect of DPDPE. Stimulation of cardiac delta1-opioid receptors with DPDPE added to perfusion saline in concentrations of 0.1 and 0.5 mg/liter decreased the incidence of reperfusion arrhythmias. Addition of DPDPE to perfusion saline in a concentration of 0.1 mg/liter prevented reoxygenation destruction of cardiomyocytes. By contrast, no cardioprotective effect of this peptide was observed at a concentration of 0.5 mg/liter in perfusion saline or when it was injected intravenously. It is concluded that the cardioprotective and antiarrhythmic effects of DPDPE are caused by activation of cardiac delta1-opioid receptors.