HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Evidence that the acute phase of ischemic preconditioning does not require signaling by the A 2B adenosine receptor.

Abstract
Ischemic preconditioning (IPC) is a protective phenomenon in which brief ischemia renders the myocardium resistant to subsequent ischemic insults. Here, we used A(2B)AR gene knock-out (A(2B)KO)/β-galactosidase reporter gene knock-in mice and the A(2B)AR antagonist ATL-801 to investigate the potential involvement of the A(2B)AR in IPC, focusing on the acute phase of protection. Cardioprotection provided by acute IPC elicited by two 3-min occlusion/3-min reperfusion cycles was readily apparent in an isolated, Langendorff-perfused mouse heart model in studies using hearts from A(2B)KO mice. IPC equivalently improved the recovery of contractile function following 20 min of global ischemia and 45 min of reperfusion in both WT and A(2B)KO hearts by ~30-40%, and equivalently decreased the release of cardiac troponin I during the reperfusion period (from 5969 ± 925 to 1595 ± 674 ng/g and 4376 ± 739 to 2278 ± 462 ng/g using WT and A(2B)KO hearts, respectively). Similarly, the infarct size-reducing capacity of acute IPC in an in vivo model of infarction was fully manifested in experiments using A(2B)KO mice, as well as in experiments using rats pretreated with ATL-801. We did observe, however, a marked reduction in infarct size in rats following administration of the selective A(2B)AR agonist BAY 60-6583 (~25% reduction at a dose of 1.0mg/kg). While supportive of its concept as a cardioprotective receptor, these experiments indicate that the mechanism of the early phase of IPC is not dependent on signaling by the A(2B)AR. We present the idea that the A(2B)AR may contribute to the later stages of IPC dependent on the induction of stress-responsive genes.
AuthorsJason E Maas, Tina C Wan, Robert A Figler, Garrett J Gross, John A Auchampach
JournalJournal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 49 Issue 5 Pg. 886-93 (Nov 2010) ISSN: 1095-8584 [Electronic] England
PMID20797398 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Aminopyridines
  • BAY 60-6583
  • Receptor, Adenosine A2B
Topics
  • Aminopyridines (pharmacology)
  • Animals
  • Blood Pressure (drug effects)
  • Heart Function Tests
  • Heart Rate (drug effects)
  • In Vitro Techniques
  • Ischemic Preconditioning, Myocardial
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction (complications, metabolism, pathology, physiopathology)
  • Myocardial Reperfusion Injury (complications, metabolism, physiopathology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Adenosine A2B (metabolism)
  • Signal Transduction (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: