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. 2003 Jul;62(7):630–634. doi: 10.1136/ard.62.7.630

Increased inflammatory activity parallels increased basal nitric oxide production and blunted response to nitric oxide in vivo in rheumatoid arthritis

H Yki-Jarvinen 1, R Bergholm 1, M Leirisalo-Repo 1
PMCID: PMC1754583  PMID: 12810424

Abstract

Background: Endothelial dysfunction, defined as loss of bioactivity of NO in the vessel wall, is thought to precede atherosclerosis.

Objective: To determine whether endothelial dysfunction characterises patients with RA and whether these patients have increased inducible nitric oxide synthase (iNOS) dependent NO production in vivo.

Methods and results: Twenty patients with RA and 33 normal subjects received intrabrachial artery infusions of endothelium dependent (acetylcholine (ACh)) and independent (sodium nitroprusside (SNP)) vasodilators to determine arterial responsiveness to NO. Basal flow and its percentage decrease by NG-monomethyl-L-arginine (L-NMMA), an inhibitor of both iNOS and endothelium dependent NOS (eNOS), was used to determine the contribution of iNOS and eNOS dependent NO to basal flow. Both SNP (p<0.01) and ACh (p<0.05) increased blood flow significantly less in patients with RA than normal subjects. Serum concentrations of TNFα were, within the RA group, inversely correlated with blood flow responses to both SNP (r=-0.67, p=0.002) and ACh (r=-0.64, p<0.005). Basal flow was significantly increased in RA and correlated within this group with serum CRP (r=0.48, p<0.05), TNFα (r=0.61, p<0.01) concentrations, and ESR (r=0.68, p<0.002). L-NMMA decreased basal flow significantly more (-34±2%) in the patients with RA than the normal subjects (-24±3%, p<0.02), suggesting in view of the blunted response to ACh, increased iNOS activity.

Conclusions: Patients with RA have a dual abnormality in NO dependent vascular function. Basal blood flow is increased in proportion to inflammatory activity and more inhibited by L-NMMA, suggesting increased iNOS activity, and responsiveness to NO is reduced.

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Figure 1.

Figure 1

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Blood flow responses (flow in experimental/control arm) to intrabrachial artery infusions of low (3 µg/min) and high (10 µg/min) doses of SNP and low (7.5 µg/min) and high (15 µg/min) doses of ACh in patients with RA (closed bars) and the normal subjects (open bars). *p<0.05, **p<0.01 for difference between groups by ANOVA.

Figure 2.

Figure 2

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Interrelationships between markers of inflammatory activity and basal flow (panels on the left) and responses to ACh or SNP (panels on the right) in patients with RA.

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