Role of β1- and β2-adrenoceptor Subtypes in Preconditioning Against Myocardial Dysfunction after Ischemia and Reperfusion

Abstract: Using an isolated nonworking rat heart model, this study investigated the role of β-adrenergic preconditioning (β-PC) to attenuate myocardial dysfunction after an ischemia/reperfusion injury. After a 20-min stabilization period, the noradrenaline depleted hearts were perfused for 5 min with isoproterenol (ISO) before 40-min global ischemia (I) followed by 30-min reperfusion (R). ISO 0.02 μM provided significant protection versus unconditioned in vivo reserpinized IR control, causing a decrease of creatine kinase (CK) release (mIU/min/g wet weight) on reperfusion in coronary effluent, a preservation of the mean coronary flow (MCF) and preservation of left ventricular function assessed by the rate-pressure product (RPP). These beneficial effects were similar to those of ischemic preconditioning (I-PC) in both nonreserpinized and reserpinized rats. Propranolol (1 μM) and atenolol (10 μM) completely suppressed the ISO preconditioning. In contrast, ICI 118,551 (2 μM), a highly selective β2-blocker, did not blunt the salutary effects of ISO on CK release and MCF preservation. These results indicate that ISO pretreatment provides a significant cardioprotection against prolonged ischemic myocardial injury. Although endogenous catecholamines are not necessary for I-PC in isolated rat hearts, cardioprotection provided by β-adrenergic stimulation is quite similar to I-PC. This significant cardioprotection is mediated less by β2-adrenoceptor than by β1-adrenoceptor activation, which seems to play a crucial role in the β-PC mechanism.