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Effect of ß-Blockers on Cardiac Function and Calcium Handling Protein in Postinfarction Heart Failure Rats^*

^* From the Departments of Respiratory Sciences (Drs. Y-L Sun and J-Y Zhou), and Cardiovascular Sciences (Drs. S-J Hu, L-H Wang, and Y Hu), The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Correspondence to: Shen-Jiang Hu, MD, PhD, Department of Cardiovascular Sciences, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China; e-mail: s0hu0001{at}hotmail.com

Objectives: The normal expression of Ca²⁺-handling protein is critical for efficient myocardial function. The present study was designed to test the hypothesis that ß-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

Methods: 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

Results: 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 ß-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). ß-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)

Conclusions: ß-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.

Key Words: Ca²⁺-adenosine triphosphatase • carvedilol • heart failure • metoprolol • phospholamban • sarcoplasmic reticulum

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