Antagonism role of adenosine in right ventricular hypertrophy induced by hypoxia in rat / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate the antagonism role of adenosine and its agonists in hypoxia-induced right ventricular hypertrophy in rat.Methods Fifty-six Sprague-Dawley rats were randomly divided into 7 groups,including normoxia control group,hypoxia control group,hypoxia plus adenosine group,hypoxia plus adenosine A1 receptor agonist(CPA) group,hypoxia plus adenosine A2 receptor agonist(NECA) group,hypoxia plus CPA and adenosine A1 receptor antagonist (DPCPX) group,hypoxia plus NECA and adenosine A2b receptor antagonist(MRS1754) group.There were 8 rats in each group.Rats in all groups except normoxia group were exposed to hypoxia for 21 days(oxygen volume concentration of 95-105 mL/L).On the 7th day,agents were continuously delivered with micro osmotic pump for 14 days.At the end of the experiment,both right ventricular to left ventricular plus septum weight[RV/(LV + S)] ratio and right ventricular to body weight (RV/BW) ratio were measured,and the expression of myosin heavy chain (β-MHC) mRNA and regulator of G protein signaling 4(RGS4) mRNA in the right ventricular myocardial tissues were detected by PCR method.Results 1.After chronic hypoxia for 21 days,the ratios of RV/(LV + S) and RV/ BW in the hypoxia control group were significantly higher than those in the normoxia control group respectively(all P ＜ 0.001) ; the ratios of RV/(LV + S) and RV/BW in the hypoxia plus adenosine group and hypoxia plus CPA group were significantly lower than those in the hypoxia control group (all P ＜ 0.05) ; the ratio of RV/(LV + S) in the hypoxia plus NECA group was significantly lower than that in the hypoxia control group(P ＜ 0.05).2.The expression level of β-MHC mRNA in the hypoxia control group was higher than that in the normoxia control group(P ＜ 0.001),and the expression level of RGS4 mRNA in the hypoxia group was lower than that in the normoxia group(P ＜ 0.001) ; the expression levels of β-MHC mRNA in the hypoxia plus adenosine group,hypoxia plus CPA group,or hypoxia plus NECA group were lower than those in the hypoxia control group (all P ＜ 0.001) ; the expression levels of RGS4 mRNA in hypoxia plus adenosine group,hypoxia plus CPA group,and hypoxia plus NECA group were higher than those in the hypoxia control group(all P ＜ 0.001).Conclusions Adenosine can attenuate hypoxia-induced right ventricular hypertrophy through RGS4 mediated pathway.