Nitric Oxide: Link between Inflammation and Endothelial Dysfunction in Rheumatoid Arthritis.

Nitric oxide (NO) plays an important role in inflammatory joint disease and endothelial function. Endothelial dysfunction has been attributed to a reduction in NO bioactivity in rheumatoid arthritis (RA). However, the relationship of NO with inflammation and endothelial dysfunction in RA has not yet been investigated. To investigate the relationship of nitrite with inflammation and endothelial dysfunction in RA. Total 28 patients satisfying 2010 Rheumatoid Arthritis Classification Criteria were recruited for the study. Serum nitrite estimation was performed by Griess reaction. Flow-mediated dilation (FMD) assessed using AngioDefender. Inflammatory disease activity measures included disease activity score of 28 joints (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Proinflammatory cytokines (TNF-α, IL-6, and IL-1) measured using standard ELISA kits. Twenty-five healthy controls matched for age and sex were included for comparison. The serum nitrite level in patients with RA was markedly elevated as compared with controls ( p  < 0.05). FMD was significantly impaired in RA patients than controls ( p  < 0.05). DAS28 was significantly higher in RA patients ( p  < 0.05). Levels of ESR, CRP, TNF-α, IL-1, and IL-6 were significantly higher in RA patients than controls ( p  < 0.05). Significant positive correlation was observed between nitrite and CRP ( r  = 0.46, p  < 0.05), TNF-α ( r  = 0.53, p  < 0.05), and inverse correlation with FMD ( r =0.62, p  < 0.05). Inflammatory disease activity and endothelial dysfunction in RA are associated with increased concentration of proinflammatory cytokines and NO. Inflammatory triggered release of cytokines induced NO production that mediates endothelial dysfunction. These findings suggest a role for NO in inflammation-induced endothelial dysfunction in RA.