Document Detail


Aldose reductase inhibitors improve myocardial reperfusion injury in mice by a dual mechanism.
MedLine Citation:
PMID:  16936455     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Aldose reductase (AR) has been implicated in the pathogenesis of diabetic complications, although the clinical efficacy of AR inhibitors has not been clearly proven. To clarify the pathophysiological role of AR in the heart, we investigated effects of AR inhibitors applied either during the pre-ischemic phase, or during the post-ischemic reperfusion phase on ischemia-reperfusion injury in isolated heart from transgenic mice overexpressing human AR. On reperfusion following global ischemia, transgenic mouse hearts exhibited lower left developed pressure, increased release of creatine kinase, and lower ATP content compared with their littermates. When inhibitors of AR were applied during the pre-ischemic phase, they significantly improved deranged cardiac function, creatine kinase release, and ATP content. On the other hand, inhibition of AR during the post-ischemic reperfusion phase did not affect cardiac performance and ATP content, but it significantly attenuated creatine kinase release and the level of thiobarbiturate-reactive substances in transgenic mouse hearts. These results suggest a dual role of AR in ischemia-reperfusion injury. Inhibition of AR during ischemia preserved generation of ATP via glycolysis, whereas inhibition during the reperfusion phase reduced myocardial injury by attenuating oxidative stress elicited by ischemic insult and reoxygenation.
Authors:
Kazumi Iwata; Kuniharu Matsuno; Toru Nishinaka; Christina Persson; Chihiro Yabe-Nishimura
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-26
Journal Detail:
Title:  Journal of pharmacological sciences     Volume:  102     ISSN:  1347-8613     ISO Abbreviation:  J. Pharmacol. Sci.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-22     Completed Date:  2006-11-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101167001     Medline TA:  J Pharmacol Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  37-46     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / biosynthesis
Aldehyde Reductase / antagonists & inhibitors*,  genetics
Animals
Creatine Kinase / metabolism
Enzyme Inhibitors / therapeutic use*
Glycolysis / physiology
L-Iditol 2-Dehydrogenase / metabolism
Mice
Mice, Transgenic
Myocardial Reperfusion Injury / drug therapy*,  physiopathology*
Oxidative Stress / drug effects
Polymers / metabolism
Sorbitol / metabolism
Thiobarbituric Acid Reactive Substances / metabolism
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Polymers; 0/Thiobarbituric Acid Reactive Substances; 0/polyol; 50-70-4/Sorbitol; 56-65-5/Adenosine Triphosphate; EC 1.1.1.14/L-Iditol 2-Dehydrogenase; EC 1.1.1.21/Aldehyde Reductase; EC 2.7.3.2/Creatine Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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