Ischemic Postconditioning Reduces Infarct Size Through the α1-Adrenergic Receptor Pathway

The alpha 1-adrenergic receptors (alpha 1-ARs) are involved in preconditioning. Given that certain intracellular pathways seem to be shared by preconditioning and postconditioning, it is possible that postconditioning could also be mediated by alpha 1-ARs. The objective was to evaluate, by analyzing infarct size, if alpha 1-ARs activation could trigger postconditioning and also determine Akt and glycogen synthase kinase 3 beta (GSK-3 beta) phosphorylation. Langendorff-perfused rat hearts were subjected to 30 minutes of ischemia and 120 minutes of reperfusion (I/R; n = 8). After 30 minutes of global ischemia, we performed 6 cycles of reperfusion/ischemia of 10 seconds each, followed by 120 minutes of reperfusion [ischemic postconditioning group (postcon); n = 9]. In another postcon group, we administered prazosin during postcon protocol (postcon + prazosin; n = 7). Finally, we repeated the I/R group, but prazosin (prazosin; n = 7), phenylephrine (PE; n = 5) and clonidine (CL; n = 6) were administered during the first 2 minutes of reperfusion. Infarct size was measured using the triphenyltetrazolium chloride technique. Total and phosphorylated Akt and mitochondrial GSK-3 beta expression were measured by Western blot. Infarct size was 58.1 +/- 5.1% in I/R. Postcon and PE reduced infarct size to 40.1 +/- 2.9% and 35.3 +/- 5.5%, respectively (P < 0.05 vs. I/R). Postcon + prazosin administration abolished the beneficial effect on infarct size (61.6 +/- 4.5%; P, 0.05 vs. postcon). Cytosolic Akt phosphorylation and mitochondrial GSK-3 beta phosphorylation were higher in the postcon and PE groups compared with the I/R and postcon + prazosin groups. Prazosin or clonidine administration did not modify neither protein expression nor infarct size. Our data demonstrate that postconditioning decrease infarct size by activation of the alpha 1-AR pathway through Akt and GSK-3 beta phosphorylation.