Prospects of Using of kappa-Opioid Receptor Agonists U-50,488 and ICI 199,441 for Improving Heart Resistance to Ischemia/Reperfusion

摘要

We studied the ability of the agonist of kappa 1-opioid receptors U-50,488 in doses of 0.1 and 1 mg/kg to simulate ischemic pre- and postconditioning of the heart and kappa-opioid receptors ICI 199,441 in a dose of 0.1 mg/kg to simulate the antiarrhythmic effect of heart preconditioning. The duration of ischemia was 10 or 45 min and the duration of reperfusion was 10 min or 2 h. Administration of 1 mg/kg U-50,488 both before ischemia and 5 min before reperfusion produced a pronounced antiarrhythmic effect. U-50,488 injected 5 min before reperfusion 2-fold reduced the ratio of infarction to risk area. Administration of ICI 199,441 in a dose of 0.1 mg/kg 15 min before ischemia produced a potent antiarrhythmic effect. Antiarrhythmic effect of kappa-opioid receptor agonists depended on activation of kappa-opioid receptors.