The role of the opioid receptors in cardioprotective adaptation to the chronic isobaric hypoxia

The role of μ, δ and к opioid receptors (OR) in cardioprotective effect of chronic normobaric hypoxia (12% O2 for 21 days) was investigated. Ischemia (20 min) was simulated by ligation of the left anterior descending coronary artery with the following reperfusion (180 min). The antagonist of all types of ORs naltrexone (5 mg/kg) was administered intravenously 25 min before ischemia. The selective δ OR antagonist TIPP(ψ) (0.5 mg/kg) was injected intravenously 25 min before ischemia, the selective μ OR blocker CTAP was used at a dose of 0.5 mg/kg intravenously 25 min before coronary artery occlusion and the selective к OR antagonist norbinaltorphimine was injected intravenously in a dose of 9 mg/kg 90 min before ischemia. Adaptation to chronic normobaric hypoxia significantly reduced (2.6 fold) the zone of necrosis/area at risk ratio. This effect was completely eliminated by the injection of naltrexone, by administration of TIPP(ψ), or by injection of CTAP, but not by norbinaltorphimine. Based on these data we can conclude that the cardioprotective effect of adaptation to chronic normobaric hypoxia is mediated through δ and μ OR activation but к opioid receptors are not involved in the infarctreducing effect of adaptation.