Gene transfer of 2 adrenergic receptor enhances cardioprotective effects of ischemic preconditioning in rat hearts after myocardial infarction

Abstract

The purpose of the present study was to determine a role of beta(2) adrenergic receptor (beta(2)AR) in ischemic preconditioning (IPC) response. Post-myocardial infarction (MI) hearts were produced by ligating the left anterior descending coronary artery for 2 weeks. Post-MI hearts were transfected with the empty virus (Empty-vivo) or beta(2)AR cDNA (beta(2)AR-vivo) by intracoronary infusion of hemagglutinating virus of Japan-liposome. Empty-vivo or beta(2)AR-vivo hearts were subjected to Langendorff perfusion as Control or beta(2)AR hearts, respectively. IPC was undertaken in Control(IPC) and beta(2)AR(IPC+beta(2)AR). After global ischemia, seven hearts in each group were reperfused and normalized left ventricular peak developed pressures (LVPDP) and creatine phosphokinase (CPK) leakage were measured. beta(2)AR gene transfection was confirmed by measuring responsiveness to isoproterenol, real time RT-PCR and immunohistochemistory. IPC preserved LVPDP and reduced CPK leakage in IPC+beta(2)AR hearts as compared with IPC hearts. LVPDP was decreased in addition to increase in CPK leakage in beta(2)AR hearts as compared with Control. Expression of beta(2)AR and responsiveness to isoproterenol were increased in beta(2)AR-vivo as compared with Empty-vivo hearts. These results indicate that beta(2)AR are required to generate IPC effects, and that beta(2)AR gene transfection enhances IPC effects in post-MI hearts.