Simvastatin prevents decreased left ventricular systolic dysfunction in non-ischemic heart failure in rabbits via inhibition of sympathetic activity

Objective:To invesitigate that simvastatin would prevent the decreased left ventricular systolic dysfunction in non-ischemic heart failure(HF) in rabbits via inhibition of sympathetic activity. Method:Non-ischemic HF was induced by combined aortic valve insufficiency and aortic constriction for 7 weeks.Rabbits were assigned to HF groups treated without(n=10) or with simvastatin(10 mg·kg-1·d-1,n=10) and control group with sham operation(n=10).Cardiac function was measured using echocardiography and catheterization.Plasma norepinephrine(NE) and brain natriuretic peptide(BNP) levels were determined using ELISA assay.Protein kinase A(PKA),total phospholamban(T-PLB) and ser16-phosphorated PLB(Pser16-PLB) abundance were determined by Western blot analysis. Result:HF rabbits with simvastatin exhibited an increased ejection fraction(P0.05),in addition to a decreased LV end-diastolic pressure(P0.05),heart rate and plasma levels of NE and BNP(P0.05),compared to HF animals without treatment.Moreover,the expression of PKA(P0.05)and the ratio of Pser16-PLB to T-PLB(P0.05) were less in HF rabbits with simvastatin compared to untreated animals with HF. Conclusion:In this study,simvastatin prevents decreased left ventricular systolic dysfunction in non-ischemic heart failure in rabbits,which might be related to the inhibition of sympathetic activity.