Changes of Left Ventricular Dysfunction and Cardiomyocyte Apoptosis in Losartan- treated Heart Failure Rats

Objective. This study is to determine whether angiotensin II (Ang II) I type receptor (ATIR) retarder inhibits cardiomyocyteapoptosis and attenuates left ventricular ( LV) dysfunction in the chronic heart failure rats. Methods.40 rats of health Sprague-Dawley (SD) were divided into 4 groups randomly. Group I was sham-operat- ed group (n = 8). Group II was heart failure group (n = 12). Group ill was losartan treated group 1 (n = 10) . Group N was losartan treated group 2 ( n = 10). Besides group I , other 3 group models of heart failure were estab- lished by part constriction of abdominal aorta of rats. After 6 weeks, group ill and group N were treated by gavage of losartan 10 mg. kg - 1 .d - 1and 30 mg. kg- 1. d - 1 respectively. Group I and group I I were gavaged by normal saline (NS). After 14 weeks, the parameters of hemodynamic and LV remodeling were detected. Ang II of plasma and cardiomyocyte were measured by radioimmuneoassay. Cardiomyocyte apoptosis were stained in situ by using TUNEL. The expression of BcI-2, Bax and procaspase-3 protein of cardiomyocyte was determined by Western blot. Results. The Left ventricular end-diastolic pressure(L VEDP) of group II was 7.2 mmHg higher than that of group I (P<O. 01)in If! weeks. Left ventricular weight( LVW)/ Body weight (BW) of group II was O. 42 mg/g higher than that of group I (P < O.01). Ang II of plasmaand cardiomyocyteof group II were 135.31 pg/ml and 94.4 pg/g higher than that of group I respectively (P < 0.01). The exponent of cardiomyocyte apoptosis of group II was 12.11 ')I()() higher than that of group I (P<O. 01). When group II comparedwith group I , the expression of cardiomyocyte Bax of group II was increased significantly while expression of BcI-2 and procaspase-3 decreased significantly(P< 0.01). When group ill and groupN compared with group II , the indexes above mention have statistical significance(P < 0.01 or P < O.05), and the index changes are related to losartan by treated dose. Con- . elusion. The results indicate that heart failure is associated with LV dysfunction and cardiomyocyteapoptosis in- volvingactivation of procaspase-3, and increased BaxlBcl-2 ratio in the rat heart. ATIR retarder attenuates LV dysfunction in the chronic heart failure rats through decreasing cardiomyocyteapoptosis and changing expressionof apoptosis-related proteins. (Life Science)ournal.2005;2(1) :49 - 54) (ISSN: 1097- 8135).