Losartan attenuates ventricular remodeling and protects heart function in rats with chronic heart failure

Objective To investigate the regulatory effect of Losartan (Los) on ventricular remodeling and cardiac function in chronic heart failure(CHF) rats induced by aorta coarctation (COA). Methods Forty Sprague-Dawley (SD) rats were randomized to receive abdominal aorta coarctation to induce CHF or sham operation and were treated with oral losartan (20 mg·kg-1·d-1) or vehicle (drinking water). As such there were four groups-COA+ vehicle group, COA+Los group, Sham+vehicle group and Sham+Los group. After 8-week treatment, ultrasound cardiography and catheterization were used to evaluate the cardiac function and left or right ventricular mass index (LVMI, RVMI). Level of myocardial hydroxyproline (HYP) was measured by chromometry. Levels of myocardium type Ⅰ and type Ⅲ collagens and their ratio were measured by ELISA. Levels of myocardial angiotensin Ⅱ(AngⅡ) and aldosterone (ALD) were measured by RIA. The morphology of myocardium was studied with HE staining, Masson trichrome staining, and ultra-structure of myocardium was also observed. Results Losartan-treated CHF rats had lower left ventricular end-diastolic pressure (LVEDP), higher left ventricular ejection fraction (LVEF) and lower left ventricle/body weight ratios, lower levels of myocardium HYP, type Ⅰ collagen, and relative ratio and lower levels of Ang Ⅱ and ALD than vehicle-treated CHF rats. By microscopy and TEM observation, the myocardial tissue in COA+ Los group showed great improvement. Conclusion Losartan attenuated ventricular remodeling and improve cardiac function in aortic constricted rats by blocking angiotensin Ⅱ to bind AT1-R and reducing angiotensin Ⅱ and aldosterone in myocardium.