We studied the effects of μ-opioid receptor activation in vivo and in vitro on the tolerance of isolated perfused rat heart to global ischemia (45 min) and reperfusion (30 min). Stimulation of μ-receptors in vivo by intraperitoneal administration of μ-opioid receptor agonist DAMGO (0.1 mg/kg) reduced reperfusion release of creatinine phosphokinase and promoted aggravation of postischemic systolic and diastolic dysfunction of the isolated heart. Activation of μ-opioid receptors in vitro by addition of selective agonist DAMGO in a concentration of 170 nM to perfusion solution had no effect on necrotic death of cardiomyocytes and aggravated reperfusion stunning of the heart.

Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to acute ischaemia/reperfusion injury. The objective of this study was to find out whether the cardioprotective effect of CNH mediated by opioid receptors is associated with preservation of mitochondrial function. Rats were adapted to CNH (12% oxygen) for 3 weeks. Isolated perfused hearts were subjected to 45 min of global ischaemia and 30 min of reperfusion; subgroups were pretreated with non-selective opioid receptor antagonist naloxone (300 nmol/L) for 10 min. Cardiac contractile function, creatine kinase activity in coronary effluent, mitochondrial respiration rate, and calcium retention capacity were assessed. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the post-ischaemic recovery of contractile function, mitochondrial state 3 and uncoupled respiration rates, and calcium retention capacity compared to the normoxic group. These protective effects were completely abolished by naloxone. The contractile recovery positively correlated with state 3 respiration and calcium retention capacity. The results suggest that the preserved mitochondrial function contributes to the protected cardiac phenotype afforded by adaptation to CNH and point to an important role of opioid receptor activation.

The active ingredient extracted from the peat humic substances was characterized by physicochemical parameters evaluated by UV- and IR-spectroscopy, titration, and elemental (C, H, N) analysis. The cardiovascular effects of this ingredient were examined on isolated Langendorff-perfused rat heart. It was found that the active substance in a concentration range of 0.01-0.1 mg/ml produced a vasodilating effect; in addition, it decreased the end-diastolic and left-ventricular developed pressures.

The role of cyclic nucleotides (cAMP, cGMP) and Ca(2+)-ATPase of the sarcoplasmic reticulum in the mechanism of cardioprotective effects of selective δ(1)- and κ(1)-opioid receptor agonists DPDPE and U-50488 was studied under conditions of global ischemia and reperfusion of isolated and perfused rat heart. Activation of both types of opioid receptors 2-fold reduced the reperfusion release of creatine phosphokinase. The cardioprotective effect of U-50488 was paralleled by a 2-fold decrease in cAMP content in the myocardium, while DPDPE did not modify the content of cAMP throughout the experiment. None of these substances changed the content of cGMP in the myocardium. The cardioprotective effect of DPDPE was not observed after inhibition of sarcoplasmic reticulum Ca(2+)-ATPase with cyclopiazonic acid. The cardioprotective effect of U-50488 was associated with reduction of cAMP level in the myocardium, while the cytoprotective effect of DPDPE was mediated by opioidergic modulation of Ca(2+) transport at the level of the sarcoplasmic reticulum.