beta-adrenoceptor stimulation-mediated preconditioning-like cardioprotection in perfused rat hearts

To determine whether adrenergic stimulation induces preconditioning-like cardioprotection, rat hearts were perfused for 2 min with either norepinephrine, phenylephrine, or isoproterenol followed by 10-min drug-free perfusion. Then the hearts were subjected to 40-min ischemia and 30-min reperfusion. Little recovery of left ventricular developed pressure (LVDP) and loss of the myocardial creatine kinase (CK) during reperfusion were observed in the drug-untreated heart. Preperfusion with norepinephrine (0.25 mu M) or isoproterenol (0.25 mu M), but not phenylephrine (10 mu M), resulted in a better recovery of LVDP in the postischemic reperfused heart and a reduction in CK release during reperfusion. A similar improvement of postischemic cardiac contractile dysfunction and CK loss was seen in the heart subjected to 5-min ischemia followed by 5-min reperfusion (ischemic preconditioning) before the prolonged period of ischemia/reperfusion. Pretreatment with timolol, a beta-adrenoceptor blocker, abolished the protective effect of norepinephrine, whereas pretreatment with bunazosin, an alpha(1)-adrenoceptor blocker, did not affect the protective effect of isoproterenol. The results suggest that a brief period of stimulation of cardiac beta-adrenoceptor exerts the preconditioning-mimetic protective effect against postischemic contractile dysfunction in perfused rat hearts.