ABSTRACT
It has been established that pretreatment with the selective mu-opioid receptor (OR) agonist DALDA (0.1 mg/kg, i.v.) or the selective delta1-OR agonists DPDPE (0.09 mg/kg) and/or (-)-TAN-67 (0.08 mg/kg) has no effect on the incidence of ventricular arrhythmias induced by a 10-min coronary artery occlusion and a 10-min reperfusion in ketamine-anesthetized rats. In contrast, the pretreatment with the selective delta2-OR agonist deltorphin II (0.12 mg/kg) and the proposed delta2-OR agonists deltorphin D (0.3 mg/kg) and/or dermorphin H (0.23 mg/kg) increases cardiac resistance to the arrhythmogenic action of acute ischemia and reperfusion. Administration of the mixed mu- and delta-OR agonist dalargin (0.12 mg/kg) 15 min before the coronary artery ligation abolished only the reperfusive ventricular fibrillation. It is concluded that peptidergic stimulation of delta2-ORs can be used as a new means of increasing cardiac tolerance to the arrhythmogenic effects of acute ischemia and reperfusion.
Subject(s)
Anti-Arrhythmia Agents/pharmacology , Myocardial Reperfusion Injury/prevention & control , Receptors, Opioid, delta/agonists , Receptors, Opioid, mu/agonists , Animals , Male , Myocardial Reperfusion Injury/complications , Myocardial Reperfusion Injury/metabolism , Organ Culture Techniques , Rats , Rats, Wistar , Ventricular Fibrillation/etiology , Ventricular Fibrillation/prevention & controlABSTRACT
Pretreatment with selective delta-opioid receptor (delta-OR) agonists decreased the level of creatine kinase in the coronary effluent of isolated rat heart during a 45-min global ischemia and a 30-min reperfusion. The effect was completely abolished after pretreatment of the delta-OR antagonist nitrindole. At the same time, pretreatment with mu-OR antagonists did not affect the level of creatine kinase in the coronary effluent. It is suggested that stimulation of the cardiac delta-OR prevents the irreversible cardiac cell damage during global ischemia and reperfusion in vitro. In contrast, the cardiac mu-OR do not play any significant role in regulation of the cardiac resistance to the pathogenic action of ischemia and reperfusion.
