Objective The present study was undertaken to investigate the protective effects of losartan on cardiomyocyte apoptosis in chronic heart failure (CHF) rats induced by banding abdominal aorta.
Methods 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 or vehicle. Plasma NE was measured by ELISA, and plasma and tissue Ang II levels were measured by 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 were assessed by Western blot.
Results Losartan-treated CHF rats had lower LVEDP (p<0.01), higher LVEF (p<0.05), lower plasma NE (p<0.05) and myocardium Ang II (p<0.05), but higher plasma Ang II (p<0.05) than vehicle-treated CHF rats. Losartan-treated CHF rats had no obviously “DNA ladder” which was the character of apoptosis, and the apoptosis index was also reduced (p<0.05) with a lower expression of Bax/Bcl-2 gene (p<0.05) and a higher protein expression of p-Akt (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.
- cardiac function
- heart failure