Involvement of opioid receptors in the cardioprotective effect of chronic normobaric hypoxia

The authors investigated the role and localization of δ 1-, δ 2-, and μ-opioid receptors in the cardioprotective effect of chronic normobaric hypoxia in rats. Chronic hypoxia modeling consisted in the exposure of animals to 12% O 2 for 21 days. This exposure led to 2.8-fold reduction in the size of myocardial infarction induced by acute 20-min coronary occlusion and 3-hour reperfusion. The protective effect of chronic hypoxia was absent in the case of intravenous infusion of the following opioid receptor (OR) blockers: 5-mg/kg naloxone methiodide, non-selective OR antagonist which does not cross the blood-brain barrier, 0.5-mg/kg TIPP (ψ), δ 1-OR antagonist; 0.3-mg/kg naltriben, δ 2-OR blocker, and 0.1-mg/ kg CTAP, μ-OR inhibitor. Adaptive cardiac tolerance to ischemia and reperfusion was present after the injection of 0.7-mg/ kg BNTX, a selective δ 1-OR antagonist. Under exposure to chronic hypoxia, the survival rate of isolated cardiomyocytes undergoing acute ischemia increased by 1.6 times. The protective effect of chronic hypoxia was absent when the incubation medium contained the following OR inhibitors: 1-μM CTAP, inhibitor of ц-opioid receptors, 0.1-μM TiPP (ψ), inhibitor of S-opioid receptors; or 10-μM naltriben, blocker of δ 2-opioid receptors. Therefore, our data suggested that the cardioprotective effect of chronic hypoxia was associated with activation of the peripheral δ 2- and μ-opioid receptors located on the membranes of cardiomyocytes.