Objective    To explore  the  etiology  of  hyperthyroid cardiomyopathy.     Methods    Forty New Zealand rabbits were randomly and equally divided into 4 groups: control group

levothyroxine(L-Thy) group

imidapril group

and valsartan group. Except the control group

rabbit model of hyperthyroidism was established by daily intraperitoneal injections of L-Thy (45 μg·kg

-1

·d

-1

× 28 d)

and the animals of later 2 groups received 0.5 mg/kg im

idapril and 8 mg/kg valsartan respectively at same period. Ventricular tissues were collected at 4 weeks. Cardic hypertrophy index

cardiomyocyte diameter

structural and ultrastructural changes were detected. Cardiac fibrosis was displayed by Masson’s staining and collagen volume fraction (CVF) was measured using pathological image analytic system. Expressions of angiotensin converting enzyme (ACE)

extracellular signal-regulated kinase (ERK)

and phosphorylated ERK (p-ERK) were evaluated with Western blot analyses.  Results    Compared with control group

rabbits of L-Thy group displayed remarkable myocardial hypertrophy

extracellular matrix fibrosis

and morphological changes in both structure and ultrastructure. Western blot analysis revealed increased protein expressions of ACE，ERK and p-ERK proteins. ERK and p-ERK expressions were correlated positively well with both cardiomyocyte diameter and CVF. Both imidapril and valsartan alleviated cardiomyocyte hypertrophy

extracellular matrix fibrosis

and structural damage induced by L-Thy. Compared with L-Thy group

expressions of lower ERK and  p-ERK were found in both imidapril and valsartan groups.    Conclusion   Renin-angiotension system (RAS) and ERK signaling pathway may play important roles in hyperthyroid cardiomyopathy. Activated RAS is possibly responsible for activation of ERK signaling pathway. Imidapril and valsartan may inhibit activation of ERK signaling pathway and retarding myocardial remodeling in hyperthyroid cardiomyopathy induced by L-Thy.