Research On Imidapril And Spironolactone Regressing Ventricular Fibrosis In Rat With Chronic Heart Failure

Objiective To investigate the effect of imidapril and spironolactone regressing ventricular fibrosis in rats with chronic heart failure and to elucidate its possible mechanism.Methods 69 Wistar male rats after abdominal aortic coarctation were randomly divided into sham-operated group, model group, imidapril group, spironolactone group , imidapril + spironolactone group and none-drug group. Cardiac mass index, myocardium collagen content , left ventricular pressure, plasma angiotensin II(AngII) and left ventricular tissue AngII, serum aldosterone(ALD) and left ventricular tissue ALD level in rat with cardiovascular fibrosis of chronic heart failure (CHF) were measured by radioimmunoassay. Sections of heart tissue was stained with HE method and the expression levels of tumor necrosis factor-α(TNF-α)and uncoupling protein-2 (UCP-2) were showed by immunohistochemistry.Results Abdominal aortic coarctation resulted in significant increase in haemodynamic parameters. Cardiac mass index, plasma and ventricular AngII, ALD ,ventricular TNF-αand UCP-2 of model group were increased (P<0.05, respectively),while those of the drug groups were decreased (P<0.05,respectively).Conclusions Myocardium collagen contents and cardiac mass index in rat with pressure overload are increased. Changes of left ventricular remodeling and cardiovascular fibrosis and collagen proliferation were observed. Imidapril and spironolactone are effective in preventing and also reversing cardiac fibrosis , and thus affording functional improvement. The effect may be related to the decrease of circulating and local AngII,ALD level and the expression levels of TNF-αand UCP-2. And using ACEI and SPI together could prevent the phenomena of "Aldosterone escape". Ventricular fibrosis plays a pivotal role in the development of chronic heart failure and is a therapeutic target.