Inducible nitric oxide synthase activity is increased in patients with rheumatoid arthritis and contributes to endothelial dysfunction
| Autor: | Kaisa M. Mäki-Petäjä, Carmel M. McEniery, Frances Hall, Joseph Cheriyan, Sharon M.L. Wallace, John Brown, A. D. Booth, Ian B. Wilkinson, Michael J. Ashby |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Endothelium Nitric Oxide Synthase Type II Arthritis Inflammation Arthritis Rheumatoid Internal medicine Humans Medicine Endothelial dysfunction omega-N-Methylarginine biology business.industry Middle Aged medicine.disease Enzyme Activation Nitric oxide synthase Forearm Endocrinology medicine.anatomical_structure Regional Blood Flow Myeloperoxidase Rheumatoid arthritis Immunology biology.protein Female Endothelium Vascular Sodium nitroprusside Inflammation Mediators medicine.symptom Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | International Journal of Cardiology. 129:399-405 |
| ISSN: | 0167-5273 |
| DOI: | 10.1016/j.ijcard.2008.02.011 |
| Popis: | 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.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.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; P0.001), 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, P0.001).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. |
| Databáze: | OpenAIRE |
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