[Expression of angiotensin converting enzyme and angiotensin II receptor in rabbits with hyperthyroid cardiomyopathy].

OBJECTIVE: To explore the pathogenesis of hyperthyroid cardiomyopathy.

METHODS: A rabbit model of hyperthyroid cardiomyopathy was reproduced by daily intraperitoneal injection of L-thyroxine (L-Thy, 45 microg x kg(-1)xd(-1)) for 28 consecutive days. Forty New Zealand rabbits were randomly divided into four groups: control group, L-Thy group, imidapril group, and valsartan group. Ventricular tissues were harvested after 4 weeks. Cardiac hypertrophy index and cardiomyocyte diameter were assessed. Cardiac fibrosis was shown by Masson's stain and collagen volume fraction (CVF) was measured using pathological image analytic system. Plasma and cardiac angiotensin II (AngII) concentration were measured with radioimmunoassay (RIAs). mRNA expression of angiotensin converting enzyme(ACE), one tape angiotensin recipient-II(AT1R) and AT2R were semi-quantified with reverse transcription-polymerase chain reaction (RT-PCR). Expression of ACE, AT1R and AT2R protein were evaluated with Western blotting analysis.

RESULTS: Compared with control group, rabbits treated with L-Thy only were found to have remarkable myocardial hypertrophy and extracellular matrix fibrosis. Increased plasma and tissue AngII were detected in L-Thy group. RT-PCR and Western blotting analysis revealed enhanced mRNA and protein expression of ACE, AT1R and AT2R. It was also demonstrated that both imidapril and valsartan alleviated cardiac hypertrophy and extracellular matrix fibrosis induced by L-Thy. Compared with L-Thy and valsartan group, imidapril group showed significantly lower plasma /tissue AngII concentration and more effective inhibition of extracellular matrix fibrosis. Imidapril did not alter the expression of ACE, AT1R or AT2R. Plasma concentration of AngII was markedly higher in valsartan group compared with L-Thy group, whereas tissue AngII concentration showed no significant difference between two groups. In valsartan group, AT1R and AT2R mRNA expressions were significantly upregulated, whereas valsartan did not change mRNA and protein expression of ACE.

CONCLUSION: Renin-angiotensin system (RAS) may play an important role in hyperthyroid cardiomyopathy. Imidapril and valsartan may exert beneficial effects on hyperthyroid cardiomyopathy via retarding myocardial remodeling.