In vitro studies suggested that
nitrite may play a cytoprotective role in
inflammation. The aim of the present clinical study was to investigate the relationship between the NO metabolites
nitrite and
nitrate and the
biomarkers of oxidative stress
3-nitrotyrosine (3-NT) and 15(S)-iso-PGF(2alpha) in patients suffering from chronic inflammatory
rheumatic diseases. In morning urine from 28 patients with different chronic inflammatory
rheumatic diseases (23-82 years of age) and from 41 healthy persons of both genders,
nitrite and
nitrate were quantitated by GC-MS, and 3-NT and 15(S)-iso-PGF(2alpha) by GC-MS/MS. Mean
creatinine-corrected urinary excretion rates of
nitrite (1.1 versus 0.19 micromol/mmol, P = 0.00012) and 3-NT (1.2 versus 0.39 nmol/mmol, P = 0.01629), but not of
nitrate (105 versus 106 micromol/mmol), were significantly elevated in
rheumatism as compared to health. Urinary excretion rate of 15(S)-iso-PGF(2alpha) did not differ between patients and healthy subjects (65 versus 69 pmol/mmol
creatinine, P = 0.48). In
rheumatism, urinary 3-NT correlated closely with
nitrite (R = 0.788, P < 0.0001) and moderately with
nitrate (R = 0.45, P < 0.016), but did not correlate with 15(S)-iso-PGF(2alpha) (R = -0.083, P = 0.68). In healthy persons there was no correlation between urinary 3-NT and
nitrite or
nitrate. Our study suggests that urinary
nitrite may represent a novel specific
biomarker of nitrative stress in chronic inflammatory
rheumatic disease. In another eight patients with chronic inflammatory
rheumatic diseases we found higher
nitrite concentrations in synovial fluid as compared to serum (1.30 versus 0.35 microM). We hypothesize that in chronic inflammatory
rheumatic diseases nitrite concentration is elevated in the inflamed joint and contributes to the inactivation of
myeloperoxidase-catalyzed production of hypochloric
acid by forming
nitryl chloride which eventually
nitrates tyrosine to form 3-NT.