CONICET | Buscador de Institutos y Recursos Humanos

ABSTRACT The α1-adrenergic receptors (α1-ARs) are involved in preconditioning. Given that certain intracellular pathways appear to be shared by preconditioning and postconditioning, it is possible that postconditioning could be also mediated by α1-ARs. The objective was to evaluate, by analyzing infarct size, if α1-ARs activation could trigger postconditioning; and also determine Akt and glycogen synthase kinase-3β (GSK-3β) phosphorylation. Langendorff-perfused rat hearts were subjected to 30 minutes of ischemia and 120 minutes of reperfusion (I/R; n=8). After 30 min of global ischemia, we performed 6 cycles of reperfusion/ischemia of 10 sec each, followed by 120 min of reperfusion (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-3β 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-3β 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 α1-AR pathway through Akt and GSK-3β phosphorylation.