e0033 Mechanisms of losartan attenuates ventricular remodelling and cardiac function in aortic banded rats with chronic heart failure

Objective To investigate the regulation of Losartan (Los) on ventricular remodelling and cardiac functioning chronic heart failure rats induced by aortic banded. Methods Sprague-Dawley (SD) rats underwent abdominal aorta coarctation to induce CHF, confirmed by ultrasound cardiograph and Catheterisation, or sham operation, followed by 8 weeks treatment with Losartan (20 mg/kg per day, orally) or vehicle (drinking water). Plasma norepinephrine (NE) was measured by ELISA, and plasma and tissue angiotensin II (Ang II) levels were measured using RIA. Cardiomyocyte apoptosis was examined by agarose gel electrophoresis and TUNEL's method. The mRNA levels of Bax and Bcl-2 were determined by RT-PCR and the protein expression of phosphorylated and total Akt(t-Akt and p-Akt) were assessed by Western blot. Results Losartan-treated CHF rats had lower left ventricular end-diastolic pressure (LVEDP) [COA+Los: (11.47±5.06) mm Hg vs COA+Vehicle: (21.18±6.56) mm Hg, p<0.01], higher left ventricular ejection fraction (LVEF) [COA+Los: (63.28±4.32)% vs COA+Vehicle: (43.27±4.25)%, p<0.05]and lower left ventricle/body weight ratios [COA+Los: (2.41±0.15) mg/g vs COA+ Vehicle: (3.12±0.18) mg/g, p<0.05], lower plasma NE[COA+Los: (682.24±64.66) pg/ml vs COA+ Vehicle : (908.24±75.10) pg/ml, p<0.05] and myocardium Ang II[COA+Los : (60.15±6.22) pg/mgprot vs COA+ Vehicle : (92.31±8.31) pg/mgprot, p<0.05], but higher plasma Ang II[COA+Los : (629.68±85.71) pg/ml vs COA+ Vehicle : (475.67±51.12) pg/ml, p<0.05] than vehicle-treated CHF rats. Losartan-treated HF rats had no obviously “DNA ladder” which was the character of apoptosis, and the apoptosis index was also reduced [COA+Los: (5.49±0.45)% vs COA+Vehicle: (9.62±0.51)%, p<0.05] with a lower express of Bax/Bcl-2 gene [COA+Los: (109.58±7.53)% vs COA+Vehicle: (136.76±8.82)%, p<0.05] and a higher protein expression of p-Akt[COA+Los: (70.80±6.40)% vs COA+Vehicle: (50.30±4.80)%, p<0.05]. Conclusion Losartan might inhibit cardiomyocyte apoptosis and improve cardiac function in aortic banded rats by blocking Ang II to bind AT1-R and promoting the activation of Akt. Conclusion Los attenuated ventricular remodelling and improve cardiac function in aortic banded rats by blocking angiotensin II to bind AT1-R and reducing angiotensin II, aldosterone and inflammatory cytokine in myocardium.