Document Detail

Reduced L-arginine transport contributes to the pathogenesis of myocardial ischemia-reperfusion injury.
MedLine Citation:
PMID:  19544385     Owner:  NLM     Status:  MEDLINE    
Myocardial injury due to ischemia-reperfusion (I-R) damage remains a major clinical challenge. Its pathogenesis is complex including endothelial dysfunction and heightened oxidative stress although the key driving mechanism remains uncertain. In this study we tested the hypothesis that the I-R process induces a state of insufficient L-arginine availability for NO biosynthesis, and that this is pivotal in the development of myocardial I-R damage. In neonatal rat ventricular cardiomyocytes (NVCM), hypoxia-reoxygenation significantly decreased L-arginine uptake and NO production (42 +/- 2% and 71 +/- 4%, respectively, both P < 0.01), maximal after 2 h reoxygenation. In parallel, mitochondrial membrane potential significantly decreased and ROS production increased (both P < 0.01). NVCMs infected with adenovirus expressing the L-arginine transporter, CAT1, and NVCMs supplemented with L-arginine both exhibited significant (all P < 0.05) improvements in NO generation and mitochondrial membrane potentials, with a concomitant significant fall in ROS production and lactate dehydrogenase release during hypoxia-reoxygenation. In contrast, L-arginine deprived NVCM had significantly worsened responses to hypoxia-reoxygenation. In isolated perfused mouse hearts, L-arginine infusion during reperfusion significantly improved left ventricular function after I-R. These improved contractile responses were not dependent on coronary flow but were associated with a significant decrease in nitrotyrosine formation and increases in phosphorylation of both Akt and troponin I. Collectively, these data strongly implicate reduced L-arginine availability as a key factor in the pathogenesis of I-R injury. Increasing L-arginine availability via increased CAT1 expression or by supplementation improves myocardial responses to I-R. Restoration of L-arginine availability may therefore be a valuable strategy to ameliorate I-R injury.
Kylie M Venardos; Amanda J Zatta; Tanneale Marshall; Rebecca Ritchie; David M Kaye
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  108     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-28     Completed Date:  2010-02-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  156-68     Citation Subset:  IM    
Copyright Information:
(c) 2009 Wiley-Liss, Inc.
Heart Failure Research Group, Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
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MeSH Terms
Arginine / metabolism*
Myocardial Reperfusion Injury / etiology*,  metabolism
Myocytes, Cardiac / metabolism
Nitric Oxide / metabolism
Oxygen Consumption
Rats, Sprague-Dawley
TRPV Cation Channels / genetics,  metabolism
Reg. No./Substance:
0/TRPV Cation Channels; 0/TRPV6 channel; 10102-43-9/Nitric Oxide; 74-79-3/Arginine

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