title: Ischemic postconditioning reduces infarct size through the α1-adrenergic receptor pathway.
abstract: The α1-adrenergic receptors (α1-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 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 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-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.
authors.affiliation: *Institute of Cardiovascular Physiopathology, Department of Pathology, School of Medicine, University of Buenos Aires, Argentina; and †Institute of Chemistry and Biological Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Bruno
authors.initials: B
authors.lastname: Buchholz
authors.forename: Verónica
authors.initials: V
authors.lastname: D Annunzio
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Giani
authors.forename: Nadezda
authors.initials: N
authors.lastname: Siachoque
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Dominici
authors.forename: Daniel
authors.initials: D
authors.lastname: Turyn
authors.forename: Virginia
authors.initials: V
authors.lastname: Perez
authors.forename: Martín
authors.initials: M
authors.lastname: Donato
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Gelpi
mesh_terms: D000818:Animals; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018340:Receptors, Adrenergic, alpha-1