Efficacy of acting κ opioid receptor for prevention of high altitude pulmonary edema in rats

Abstract

Objective To evaluate the efficacy of acting κ opioid receptor for prevention of high altitude pulmonary edema (HAPE) in rats.Methods Forty male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 5 groups (n =8 each) using a random number table:control group (group C),hypobaric hypoxia group (group H),normal saline + hypobaric hypoxia group (group NH),U50488H (a selective kappa-opioid receptor agonist) + hypobaric hypoxia group (group UH),and nor-binaltorphimine (norBNI,a selective kappa-opioid receptor antagonist) + U50488H + hypobaric hypoxia group (group NUH).The rats were put into the hyperbaric chamber and exposed to hypobaric hypoxia (atmospheric pressure 355 mmHg,partial pressure of oxygen 74 mmHg) for 2 days to induce HAPE.At 3 days before HAPE,normal saline 0.5 ml,U50488H 1.25 mg/kg,and nor-BNI 2.0 mg/kg were injected intraperitoneally once a day in NH,UH,and NUH groups,respectively,and in addition U50488H 1.25 mg/kg was injected intraperitoneally 10 min later in NUH group.After 2 h exposure to hypobaric hypoxia,mean pulmonary artery pressure (mPAP) was detected,and arterial blood samples were collected for determination of serum malondialdehyde (MDA) and erythropoietin (EPO) levels.The rats were then sacrificed and lungs were removed for microscopic examination and for determination of the levels of nitric oxide (NO),inducible nitric oxide synthase (iNOS),MDA,superoxide dismutase (SOD),endothelin-1 (ET-1),thromboxane B2 (TXB2),and 6-keto-prostaglandin F1α (6-keto-PGF1α) in lung tissues.Lung water content and TXB2/6-keto-PGF1α ratio was calculated.Results Compared with group C,mPAP,lung water content,ET-1,MDA,TXB2 and 6-keto-PGF1α levels,TXB2/6-ketoPGF1α ratio,and serum MDA and EPO levels were significantly increased,and iNOS,NO and SOD levels were decreased in the other four groups (P ＜ 0.05).Compared with group H,mPAP,lung water content,ET-1,MDA,TXB2 and 6-keto-PGF1α levels,TXB2/6-ketoPGF1α ratio and serum MDA and EPO levels were significantly decreased,and iNOS,NO and SOD levels were increased in UH group (P ＜ 0.05),and no significant changes were found in the indexes mentioned above in NH and NUH groups (P ＞ 0.05).The pathological changes of lung tissues were significantly attenuated in group UH as compared with H group.Conclusion Acting κ opioid receptor can produce prevention for HAPE in rats,and inhibition of lipid peroxidation and correction of the imbalance between vasoconstrictive factors and vasodilative factors may be involved in the mechanism. Key words: Receptors, opioid, kappa; Pulmonary edema; Altitude sickness