Tohoku J. Exp. Med., 2009, 219(2)

Pretreatment with B-type Natriuretic Peptide Protects the Heart From Ischemia-Reperfusion Injury by Inhibiting Myocardial Apoptosis

BING WU,^1,2 HONG JIANG,¹ RONG LIN,² BO CUI,¹ HUAZHI WEN¹ and ZHIBING LU¹

¹Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
²Department of Cardiology, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, China

The therapy for acute myocardial infarction (AMI) has been improved; yet, AMI remains a major cause of death and heart failure in industrialized countries. B-type natriuretic peptide (BNP), a hormone secreted from the heart, has been shown cardioprotective effects during myocardial ischemia/reperfusion. In the present study, we aimed to examine whether BNP could inhibit myocardial apoptosis during ischemia/reperfusion. Rabbits were randomly divided into three groups (12 animals for each group): sham-operated control and ischemia-reperfusion animals with or without BNP treatment. Occlusion of the left circumflex coronary for 45 min was followed by 3-h reperfusion with infusion of physiological saline (untreated group) or BNP (treated group) starting 5 min before reperfusion and throughout the whole reperfusion. The infarct size, measured by triphenyltetrazolium chloride staining, was reduced by 44% with BNP treatment (P < 0.01). Accordingly, serum levels of creatine kinase and lactate dehydrogenase were markedly reduced in BNP-treated group (P < 0.05) compared with the untreated group. BNP significantly attenuated apoptotic cells (TUNEL-positive cardiomyocyte nuclei) in the myocardium (P < 0.01). The BNP-mediated attenuation of apoptosis was associated with the increased expression of an anti-apoptotic protein Bcl-2 and the reduced expression of a pro-apoptotic protein Bax. Moreover, BNP treatment significantly decreased the magnitude of caspase-3 activation caused by myocardial ischemia-reperfusion. In conclusion, pretreatment with BNP shortly before the onset of reperfusion not only reduces necrosis, but also attenuates myocardial apoptosis. BNP appears to be an ideal pharmacological agent applied as an adjuvant therapy to current myocardial reperfusion strategies.

keywords —— B-type natriuretic peptide; reperfusion injury; apoptosis; Bcl-2 family; caspase-3.

© 2009 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2009, 219, 107-114

Correspondence: Hong Jiang, Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan 430060, PR China.

e-mail: jianghong1958@gmail.com