Effects of A_(2a) adenosine receptor on hypoxic pulmonary hypertension in rats treated with salidroside

AIM:To study the protective effect of A2a adenosine receptor(A2aAR) on hypoxic pulmonary hypertension in the rats treated with salidroside.METHODS: Sprague-Dawley rats were randomly divided into 6 groups: normal control group,hypoxia group,hypoxia+salidroside(low dose) group,hypoxia+salidroside(median dose) group,hypoxia+salidroside(high dose) group,and hypoxia+CGS-21680(a selective agonist of A2aAR) group.Pulmonary hypertension in the rats was produced for 4 weeks.Mean pulmonary artery pressure(mPAP),mean carotid arterial pressure(mCAP) and the weight ratio of right ventricle/(left ventricle+septum) were measured.The expression of A2aAR in the pulmonary arterioles was determined by immunohistochemistry and in situ hybridization.The mRNA expression of A2aAR in the lung tissues was detected by real-time RT-PCR.The protein level of A2aAR in the lung tissues was analyzed by Western blotting.RESULTS: The mPAP in hypoxia group was significantly higher than that in normal control group.The mPAP in hypoxia+salidroside(high dose) group and CGS-21680 group was significantly lower than that in hypoxia group.RV/(LV+S) in hypoxia group were significantly higher than that in normal control group.RV/(LV+S) in hypoxia+salidroside(median dose) group,hypoxia+salidroside(high dose) group and CGS-21680 group were lower than that in hypoxia group.The ratio of vessel wall area/vessel total area(WA/TA) in hypoxia group was significantly higher than that in normal control group.WA/TA in hypoxia+salidroside(low dose) group,hypoxia+salidroside(median dose) group,hypoxia+salidroside(high dose) group and CGS21680 group were obviously lower than that in hypoxia group.The expression of A2aAR was significantly higher in hypoxia group than that in normal control group.The expression of A2aAR in hypoxia+salidroside(high dose) group and CGS-21680 group was obviously higher than that in hypoxia group.CONCLUSION: The A2aAR attenuates pulmonary vessel remodeling and pulmonary hypertension induced by hypoxia.Salidroside protects the pulmonary vessel from remodeling and inhibits the development of hypoxia-induced pulmonary hypertension by up-regulation of A2aAR expression.