Participation of central and peripheral opioid receptors in mechanisms of arrhythmogenesis

This study was designed to determine the role of opioid receptors (OR) in arrhythmogenesis in the models of epinephrine-, aconitine- and CaCl₂-induced arrhythmias in rats. The OR ligands were injected icv at a dose of 20 nmol/rat or intravenously (iv) 30 min before the induction of arrhythmias. Mu-OR agonists (DAGO, DALDA) had antiarrhythmic effects with systemic and icv administration. Kappa-OR agonists (spiradoline, U-504488) exhibited antiarrhythmic properties only with iv administration, but icv infusion produced proarrhythmic effects. Ligands of central delta-ORs (DTLET, DSLET, DPDPE, DADLE) increased cardiac resistance to arrhythmogenic influences, but iv administration delta-OR agonists did not affect arrhythmias. The proarrhythmic effects of central administration of kappa-OR agonists were associated with the activation of sympathetic nervous system and were completely eliminated by hexomethonium (10 mg/kg, iv). Antiarrhythmic effects of mu-OR agonists injected icv were completely eliminated by atropine (iv and icv). The mechanisms of increased cardiac resistance to arrythmogenic agents after peripheral mu-OR activation appear to be unclear.