Document Detail


Inhibition of the cardiac electrogenic sodium bicarbonate cotransporter reduces ischemic injury.
MedLine Citation:
PMID:  11738055     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Although it is believed that sodium-driven acid-base transport plays a central role in the development of the reperfusion injury that follows cardiac ischemia, research to date has demonstrated only a role for Na(+)/H(+) exchange (NHE). However, Na(+)-driven HCO(-)(3) transport, which is quantitatively as important as NHE in cardiac cells, has not been examined. METHODS AND RESULTS: Here the results show that a neutralizing antibody raised against the human heart electrogenic Na(+)/HCO(3)(-) cotransporter (hhNBC) blocked the recovery of pH after acidic pulse both in HEK-293 cells expressing hhNBC and in rat cardiac myocytes demonstrating the presence of an electrogenic NBC in rat cardiac myocytes similar to hhNBC. Administration of anti-NBC antibody to ischemic-reperfused rat hearts markedly protects systolic and diastolic functions of the heart during reperfusion. Furthermore, using a quantitative real-time RT-PCR (TaqMan) and Western blot analysis we demonstrated that in human cardiomyopathic hearts, mRNA and protein levels of hhNBC increase, whereas mRNA levels of the electroneutral Na(+)/HCO(3)(-) cotransporter (NBCn1) remain unchanged. CONCLUSION: Our data provide evidence that inhibition of hhNBC, whose role in cardiac pathologies could be amplified by overexpression, represents a novel therapeutic approach for ischemic heart disease.
Authors:
N Khandoudi; J Albadine; P Robert; S Krief; I Berrebi-Bertrand; X Martin; M O Bevensee; W F Boron; A Bril
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cardiovascular research     Volume:  52     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2001-12-12     Completed Date:  2002-02-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  387-96     Citation Subset:  IM    
Affiliation:
GlaxoSmithKline Laboratoires Pharmaceutiques, 4 Rue du Chesnay-Beauregard, BP 96205, 35762 Cédex, Saint-Grégoire, France. nassirah_khandoudi@sbphrd.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / pharmacology*
Blotting, Western
Cell Line
Cells, Cultured
Gene Expression
Humans
Hydrogen-Ion Concentration
L-Lactate Dehydrogenase / analysis
Male
Myocardial Reperfusion Injury / metabolism*
Myocardium / metabolism*
Perfusion
RNA, Messenger / analysis
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Sodium-Bicarbonate Symporters / immunology,  metabolism,  physiology*
Sodium-Hydrogen Antiporter / metabolism
Grant Support
ID/Acronym/Agency:
DK30344/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/RNA, Messenger; 0/Sodium-Bicarbonate Symporters; 0/Sodium-Hydrogen Antiporter; EC 1.1.1.27/L-Lactate Dehydrogenase
Comments/Corrections
Comment In:
Cardiovasc Res. 2001 Dec;52(3):339-44   [PMID:  11738051 ]

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


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