Effect of beta-blockers on cardiac function and calcium handling protein in postinfarction heart failure rats

The normal expression of Ca2+-handling protein is critical for efficient myocardial function. The present study was designed to test the hypothesis that beta-blocker treatment may attenuate left ventricular (LV) remodeling and cardiac contractile dysfunction in the failing heart, which may be associated with alterations of Ca2+-handling protein

We investigated the change of LV remodeling and function in a rat model of heart failure due to myocardial infarction (MI) with or without carvedilol (30 mg/kg/d) or metoprolol (60 mg/kg/d) treatment for 6 weeks (n = 9 in the MI plus carvedilol group, and n = 8 in every other group). The expression of messenger RNA and proteins of sarcoplasmic reticulum Ca2+-adenosine triphosphatase (SERCA) and phospholamban in cardiomyocytes of all rats were also measured

There was significant LV remodeling and cardiac contractile dysfunction in MI rats. The messenger RNA and protein expression of SERCA were down-regulated (p < 0.01), but the expression of phospholamban messenger RNA and protein were up-regulated (p < 0.01) in MI rats compared to sham-operated rats. After the treatment with beta-blockers, LV remodeling and function were clearly improved. Carvedilol was better in attenuating the weight of the LV and the relative weight of the right ventricle than metoprolol (p < 0.05). beta-Blockers restored the low expression of SERCA (p < 0.05) but showed no effect on phospholamban expression (p > 0.05). Moreover, carvedilol induced a more significant improvement of SERCA expression than metoprolol (p < 0.05)

Beta-blockers are effective in preventing LV remodeling and cardiac contractile dysfunction in the failing heart. The molecular mechanism may be related to normalization of SERCA expression.