Document Detail


Inducible nitric oxide synthase activity is increased in patients with rheumatoid arthritis and contributes to endothelial dysfunction.
MedLine Citation:
PMID:  18571252     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Recent in vitro studies suggest that inducible nitric oxide synthase (iNOS) activity mediates endothelial dysfunction. Rheumatoid arthritis (RA) is a chronic inflammatory condition and is associated with endothelial dysfunction and increased risk of cardiovascular disease. The aim of the study was to establish the contribution of iNOS to endothelial function. METHODS: Forearm blood flow (FBF) was measured during intra-arterial infusions of acetylcholine (ACh), sodium nitroprusside (SNP), N(G)-monomethyl-l-arginine (l-NMMA) and aminoguanidine (AG) in 12 RA patients and 13 healthy control subjects. Levels of C-reactive protein (CRP) and myeloperoxidase (MPO) were assessed. FBF data are presented as mean percentage changes in the ratio (infused/control arm) of FBF + or - SEM. RESULTS: FBF response to ACh was reduced in patients with RA compared to controls (179 + or - 29 v. 384 + or - 72%, respectively; P=0.01), but SNP response was not (P=0.5). FBF response to AG differed between patients and controls (-15 + or - 2% v. 13 + or - 4%, respectively; P<0.001), whereas the response to l-NMMA did not (P=0.4). In a multiple regression model log CRP, AG response and LDL were found to be independent predictors of endothelial function (R(2)=0.617, P<0.001). CONCLUSION: RA patients have endothelial dysfunction and increased iNOS activity in comparison to controls. Furthermore, CRP and iNOS activity were independently associated with endothelial function. Our data demonstrates that inflammation is a key mediator in a process of endothelial dysfunction possibly via activation of iNOS and increased production of MPO.
Authors:
Kaisa M Mäki-Petäjä; Joseph Cheriyan; Anthony D Booth; Frances C Hall; John Brown; Sharon M L Wallace; Mike J Ashby; Carmel M McEniery; Ian B Wilkinson
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-20
Journal Detail:
Title:  International journal of cardiology     Volume:  129     ISSN:  1874-1754     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2010-02-23     Completed Date:  2010-09-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  399-405     Citation Subset:  IM    
Affiliation:
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Box 110, Cambridge, UK. km391@cam.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Arthritis, Rheumatoid / enzymology*,  physiopathology*
Endothelium, Vascular / enzymology*,  physiopathology*
Enzyme Activation / physiology
Female
Forearm / blood supply
Humans
Inflammation Mediators / metabolism,  physiology
Male
Middle Aged
Nitric Oxide Synthase Type II / antagonists & inhibitors,  metabolism*
Regional Blood Flow / physiology
omega-N-Methylarginine / pharmacology
Grant Support
ID/Acronym/Agency:
//British Heart Foundation
Chemical
Reg. No./Substance:
0/Inflammation Mediators; 17035-90-4/omega-N-Methylarginine; EC 1.14.13.39/Nitric Oxide Synthase Type II

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