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ISCHEMIC POSTCONDITIONING REDUCES INFARCT SIZE THROUGH THE α-1 ADRENERGIC RECEPTOR PATHWAY.
MedLine Citation:
PMID:  24406486     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Bruno Buchholz; Verónica D Annunzio; Jorge F Giani; Nadezda Siachoque; Fernando P Dominici; Daniel Turyn; Virginia Perez; Martín Donato; Ricardo J Gelpi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-8
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  -     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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