Combination of simvastatin and losartan attenuates left ventricular myocardial fibrosis after pressure overload state in rats

Aim To investigate the effect of the combination of simvastatin and losartan on myocardial fibrosis after pressure overload state in rats.Methods The heart failure model was induced by descending aortic constriction(DAC).120 SD rats were randomized into 6 groups:normal control group,control sham group,model group,losartan group,simvastatin group,combination of losartan and simvastatin group.After drug treatment for 35 days,hearts were excised and weighed,the serum BNP level was measured by ELISA,mRNA levels of Collagen-Ⅰ and Collagen-Ⅲ were measured by RT-PCR,and Collagen-Ⅰ mRNA/Collagen-Ⅲ mRNA ratio was calculated as well.Collagen was quantified by Masson staining.Results Histological analysis revealed myocardial fibrosis in left ventricular sections.HW/BW ratio and LV Weight/LV weight ratio in DAC rats,as well as the BNP all increased significantly(all,P0.01),which were inhibited by drug treatment(all,P0.05).Especially combination of two drugs(P0.05).RT-PCR showed that Collagen-Ⅰ and Collagen-Ⅲ expressions,as well as Collagen-Ⅰ mRNA/Collagen-Ⅲ mRNA ratio increased significantly(all,P0.05)in DAC rats and drug treatment downregulated them significantly(all,P0.05).Combination of two drugs showed more reduction than single drug treatment significantly(P0.05).Conclusions These findings indicate that the combination of simvastatin and losartan can attenuate the development of left ventricular myocardial fibrosis after pressure overload state more than the single drug treatment.