Background: In vitro studies suggest that inducible nitric oxide synthase (iNOS) activity mediates endothelial dysfunction, but the role of iNOS in the process of arterial stiffening (AS) and endothelial function (EF) in vivo is unknown. Rheumatoid arthritis (RA) is a chronic inflammatory condition and as such can provide an interesting model to study this. The aim was to establish the contribution of iNOS to AS and EF.

Methods: Forearm blood flow (FBF) was measured during intra-arterial infusions of acetylcholine (ACh), sodium nitroprusside (SNP), N-monomethyl-L-arginine (L-NMMA) and aminoguanidine (AG), a selective iNOS inhibitor, in 12 RA patients and 13 control subjects. Aortic pulse wave velocity (aPWV) was also assessed.

Results: FBF response to ACh was reduced in RA patients compared to controls (384 ± 72 v. 179 ± 29%, respectively; P = 0.01), whereas SNP response was preserved (P = 0.5). AG reduced FBF in RA patients, but not in controls (−15 ± 2% v. 13 ± 4%, P<0.001), while the response to L-NMMA was not different between the groups (P = 0.4). RA patients had higher aPWV than controls (P = 0.01). In multiple regression models logCRP, LDL and AG response were found to be independent predictors of EF (R² = 0.617, P<0.001), and EF, AG response, and age independently predicted aPWV (R² = 0.616, P<0.001).

Conclusion: RA patients have increased aPWV and iNOS activity, and blunted EF in comparison to controls. iNOS activity independently predicts aPWV and EF. Additionally, aPWV is independently associated with EF. However, the causal relationship between these conditions remains unclear; possibly they exist in parallel, driven by common risk factors, such as inflammation.