Document Detail

Evidence that the acute phase of ischemic preconditioning does not require signaling by the A 2B adenosine receptor.
MedLine Citation:
PMID:  20797398     Owner:  NLM     Status:  MEDLINE    
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.
Jason E Maas; Tina C Wan; Robert A Figler; Garrett J Gross; John A Auchampach
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-24
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  49     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2011-01-18     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  886-93     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Department of Pharmacology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
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MeSH Terms
Aminopyridines / pharmacology
Blood Pressure / drug effects
Heart Function Tests
Heart Rate / drug effects
Ischemic Preconditioning, Myocardial*
Mice, Inbred C57BL
Myocardial Infarction / complications,  metabolism,  pathology,  physiopathology
Myocardial Reperfusion Injury / complications,  metabolism,  physiopathology
Rats, Sprague-Dawley
Receptor, Adenosine A2B / metabolism*
Signal Transduction* / drug effects
Grant Support
R01 HL 008311/HL/NHLBI NIH HHS; R01 HL077707/HL/NHLBI NIH HHS; R01 HL077707-05W1/HL/NHLBI NIH HHS; R01 HL077707-07/HL/NHLBI NIH HHS; R37 HL074314/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Aminopyridines; 0/BAY 60-6583; 0/Receptor, Adenosine A2B

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