Inducible nitric oxide synthase activity is increased in patients with rheumatoid arthritis and contributes to endothelial dysfunction

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

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    45 Citations (Scopus)


    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), NG-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 ± SEM. Results: FBF response to ACh was reduced in patients with RA compared to controls (179 ± 29 v. 384 ± 72%, respectively; P = 0.01), but SNP response was not (P = 0.5). FBF response to AG differed between patients and controls (- 15 ± 2% v. 13 ± 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 (R2 = 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.

    Original languageEnglish
    Pages (from-to)399-405
    Number of pages7
    JournalInternational Journal of Cardiology
    Issue number3
    Publication statusPublished - 13 Oct 2008


    • Endothelial dysfunction
    • Forearm blood flow
    • Inflammation
    • Nitric oxide synthase
    • Rheumatoid arthritis


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