Document Detail


Effects of targeted deletion of A1 adenosine receptors on postischemic cardiac function and expression of adenosine receptor subtypes.
MedLine Citation:
PMID:  16679400     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To examine ischemic tolerance in the absence of A(1) adenosine receptors (A(1)ARs), isolated wild-type (WT) and A(1)AR knockout (A(1)KO) murine hearts underwent global ischemia-reperfusion, and injury was measured in terms of functional recovery and efflux of lactate dehydrogenase (LDH). Hearts were analyzed by real-time RT-PCR both at baseline and at intervals during ischemia-reperfusion to determine whether compensatory expression of other adenosine receptor subtypes occurs with either A(1)AR deletion and/or ischemia-reperfusion. A(1)KO hearts had higher baseline coronary flow (CF) and left ventricular developed pressure (LVDP) than WT hearts, whereas heart rate was unchanged by A(1)AR deletion. After 20 min of ischemia, CF was attenuated in A(1)KO compared with WT hearts, and this reduction persisted throughout reperfusion. Final recovery of LVDP was decreased in A(1)KO hearts (54.4 +/- 5.1 vs. WT 81.1 +/- 3.4% preischemic baseline) and correlated with higher diastolic pressure during reperfusion. Postischemic efflux of LDH was greater in A(1)KO compared with WT hearts. Real-time RT-PCR demonstrated the absence of A(1)AR transcript in A(1)KO hearts, and the message for A(2A), A(2B), and A(3) adenosine receptors was similar in uninstrumented A(1)KO and WT hearts. Ischemia-reperfusion increased A(2B) mRNA expression 2.5-fold in both WT and A(1)KO hearts without changing A(1) or A(3) expression. In WT hearts, ischemia transiently doubled A(2A) mRNA, which returned to preischemic level upon reperfusion, a pattern not observed in A(1)KO hearts. Together, these data affirm the cardioprotective role of A(1)ARs and suggest that induced expression of other adenosine receptor subtypes may participate in the response to ischemia-reperfusion in isolated murine hearts.
Authors:
R Ray Morrison; Bunyen Teng; Peter J Oldenburg; Laxmansa C Katwa; Jurgen B Schnermann; S Jamal Mustafa
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-05-05
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  291     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-15     Completed Date:  2006-11-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1875-82     Citation Subset:  IM    
Affiliation:
Division of Critical Care Medicine, St. Jude Children's Research Hospital, 332 N. Lauderdale St., MS 734, Memphis, TN 38105, USA. ray.morrison@stjude.org
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MeSH Terms
Descriptor/Qualifier:
Animals
Coronary Vessels / physiology
Female
Gene Deletion
Gene Expression Regulation / physiology
Lactate Dehydrogenases / metabolism
Male
Mice
Mice, Knockout
Myocardial Contraction / physiology
Myocardial Ischemia / genetics*,  metabolism
Myocardium / metabolism*
RNA, Messenger / genetics,  metabolism
Receptor, Adenosine A1 / genetics*,  metabolism
Receptor, Adenosine A2A / genetics*,  metabolism
Receptor, Adenosine A2B / genetics*,  metabolism
Receptor, Adenosine A3 / genetics*,  metabolism
Regional Blood Flow / physiology
Reperfusion Injury / physiopathology*
Vasodilation / physiology
Grant Support
ID/Acronym/Agency:
HL-074001/HL/NHLBI NIH HHS; HL-27339/HL/NHLBI NIH HHS; HL-60047/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Receptor, Adenosine A1; 0/Receptor, Adenosine A2A; 0/Receptor, Adenosine A2B; 0/Receptor, Adenosine A3; EC 1.1.-/Lactate Dehydrogenases

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