Involvement of adenosine in cardioprotective effect of catecholamine preconditioning in ischemia-reperfused heart of rat

ABSTRACT

Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of alpha- or beta-adrenergic agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine A1 or A2 receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a beta-agonist, isoproterenol(10-9 ~ 10-7 M) markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an alpha-agonist, phenylephrine pretreatment, but much higher concentration(10-4 M) was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a beta1-adrenergic receptor antagonist, atenolol, but not by an alpha1-antagonist, prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective A1-adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of beta1-adrenergic receptor pathway, and that adenosine is involved in this cardioprotective effect.