The role of adenosine and ATP-sensitive potassium channels in the protection afforded by ischemic preconditioning against the post-ischemic endothelial dysfunction in guinea-pig hearts

The role of adenosine and ATP-sensitive potassium channels (K-ATP) in the mechanism of ischemic preconditioning (LPC)-induced protection against the post-ischemic endothelial dysfunction was studied. Langendorff-perfused guinea-pig hearts were subjected either to 40 min of global ischemia and 40 min reperfusion or were preconditioned prior to the ischemia/reperfusion with three cycles of either 5 min ischemia/5 min reperfusion (IPC) or 5 min infusion/5 min wash-out of adenosine, adenosine A. receptor agonist, N-6-cyclohexladenosine (CHA) or K-ATP opener. pinacidil. The magnitude of coronary flow reduction caused by NO-synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), served as an index of a basal endothelium-dependent vasodilator tone. Coronary overflows produced by a bolus of acetylcholine (ACh) and sodium nitroprusside (SNP) were used as measures of agonist-induced endothelium-dependent and endothelium-independent vascular function, respectively. The coronary flow. LVDP, ACh response and L-NAME response were reduced by 8, 32, 41 and 54%, respectively, while SNP response was not changed in the hearts subjected to ischemia/reperfusion. ACh response was fully restored, L-NAME response was partially restored, and SNP response was not affected in the hearts subjected to IPC. The post-ischemic recoveries of coronary flow and LVDP were not improved by IPC. The protective effect of TPC on the ACh response was mimicked by adenosine. CHA, and pinacidil. The protective effect of IPC, CHA and pinacidil was abolished by K-ATP antagonist. glibenclamide. The IPC protection was affected neither by a non-specific adenosine antagonist, 8-p-sulfophenyltheophylline, nor by a specific adenosine A, receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Our data indicate that: (1) TPC affords endothelial protection in the mechanism that involves activation of K-ATP, but not adenosine A(1) receptors; (2) exogenous adenosine and A(1) receptor agonist afford the protection, which might be of a potential clinical significance; (3) the endothelial dysfunction is not involved in the mechanism of myocardial stunning in guinea-pig hearts. (C) 1998 Academic Press