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: Bruno Buchholz, Verónica D Annunzio, Jorge F Giani, Nadezda Siachoque, Fernando P Dominici, Daniel Turyn, Virginia Perez, Martín Donato, Ricardo J Gelpi
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 63 Issue 6 Pg. 504-11 (Jun 2014) ISSN: 1533-4023 [Electronic] United States
• PMID: 24406486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Adrenergic, alpha-1

Topics

• Animals
• Ischemic Postconditioning (methods)
• Male
• Myocardial Infarction (metabolism, therapy)
• Rats
• Rats, Wistar
• Receptors, Adrenergic, alpha-1 (metabolism)
• Signal Transduction (physiology)