Effect Of Atorvastatin On Right Ventricular Hypertrophy In Rats With Monocrotaline-induced Pulmonary Hypertension

Objective：To investigate the effect of atorvastatin on pulmonary artery pressure andright ventricular hypertrophy in rats with monocrotaline-induced pulmonaryhypertension；To discuss the role of connexin43(Cx43)and cardiac troponin T(cTn-T)onthe right ventricular hypertrophy caused by pulmonary hypertension，and the effect ofatorvastatin on Cx43、cTnT in rats with monocrotaline-induced pulmonary hypertension.Methods:Forty male SD rats were randomly divided into five groups with eighteach group： control group(Ctr group),pulmonary hypertension group(MCTgroup),atorvastatin group(Ato1group),atorvastatin group(Ato2group),diltiazemgroup(Dil group).The rats in MCT group,Ato1group,Ato2group,Dil group were injectedwith50mg/kg of MCT subcutaneously,and the rats in Ctr group were injected with1ml ofsaline.Since the next day after MCT injected,Atorvastatin（10mg/kg/d）was administeredby gavage to rats in Ato1group,Atorvastatin （20mg/kg/d） in Ato2group,diltiazem(25mg/kg/d)in Dil group,respectively;and distilled water was given bygavage to rats in Ctr group and MCT group.Three weeks after MCT injected,meanpulmonary artery pressure(mPAP)and right ventricular systolic pressure(RVSP)wasmeasured by right heart catheterizationthe.The concentration of cTnT plasma wasdetected by Enzyme-linked immunosorbent assay(ELISA);Right ventricular hypertrophyindex(RVHI)was calculated[RVHI=RV/(LV+S)];Hematoxylin-eosin(HE)staining wereobserved for the morphological changes of right ventricular myocardium;Immunohistochemistry were observed for the change of Cx43expression inright ventricular.Result:The mean pulmonary artery pressure(mPAP),right ventricular systolicpressure(RVSP),Right ventricular hypertrophy index(RVHI)and cTnT in MCT groupwere significantly increased than that in Ctr group(P<0.001),each interventiongroup(Ato1group,Ato2group,Dil group)were decreased significantly than that in MCTgroup(P<0.001),but decreased than that in Ctr group(P<0.001);There was no significantlydifference on mPAP and RVSP between intervention groups(P>0.05);The RVHI in Ato2group was higher than that in Ato1group(P<0.001)However,there was no significantdifference between Ato2group and Dil group(P>0.05);cTnT in Atro-H group was lowerthan that in Ato1group(P<0.01),but there was no significant difference between Ato2group and Dil group(P>0.05);The changes of right ventricular in MCT group were rightventricular hypertrophy,muscle fiber disorders， inflammatory cell infiltration andconnective tissue proliferation as compared with Ctr group； and the changes inintervention groups were between MCT group and Ctr group；The expression of Cx43onright ventricular in MCT group were decreased as well compared with Ctrgroup(P<0.001)，and that changes in intervention group were between MCT group andCtr group(P<0.05).Conclusion:Atorvastatin can improve monocrotaline-induced pulmonary arterypressure and right ventricular hypertrophy,decrease concentration of plasma cTnT andright ventricular Cx43expression.The improvement on right ventricular hypertrophy andcTnT by atorvastatin are correlated with dosage;Atorvastatin lower the abnormalexpression of Cx43on right ventricular myocardium，the mechanism of which is thereverse of right ventricular remodeling with Atorvastatin.