Abstract
The objective of this research was to determine, if NO production, as measured in the serum and urine, is increased in patients with rheumatoid arthritis. Forty-seven patients with RA were recruited in the study and subdivided into inactive and active disease (24 and 23 patients, respectively). Twenty-eight healthy individuals served as controls and nine patients with gastroenteritis were studied to validate the technique of measurement of NO production. Nitrite and citrulline were measured by spectrophotometry, as surrogate markers of NO production. It was found that serum nitrite and citrulline levels of patients with gastroenteritis were not significantly different from controls and the two subgroups of RA. Urine nitrite and citrulline levels were significantly higher in patients with gastroenteritis as compared to the two subgroups of RA and controls (p; > 0.001). Serum and urine nitrite levels of patients with active RA were higher than controls and patients with inactive disease (p > 0.05). Serum citrulline levels were not significantly different among the two subgroups of patients with RA. However, they were significantly higher in patients with active disease as compared with controls (p > 0.05). Urinary citrulline levels were significantly higher among patients with active disease as compared to controls and patients with inactive RA (p > 0.05). It is therefore suggested that urinary nitrite and citrulline levels can be useful for the measurement of NO production and are associated with active disease in patients with RA.
This is a preview of subscription content, log in via an institution to check access.
References
S. Moncada and A. Higgs (1993). The L-arginine: nitric oxide pathway,New Eng J. Med. 329, 2002–2012.
M. Stefanovice-Racic, L. Shakier and C. H. Evans (1993). Nitric oxide and arthritis,Arthritis Rheum,36, 1036–1044.
F. Y. Liew, Y. Li, A. Severn et al. (1991). A possible novel pathway of regulation by murine T-helper cells of Th-l cell activity via the modulation of induction of nitric oxide synthase on macrophages,Eur J. Immunol. 21, 2489–2494.
J. B. Hibbs, Z. Vavrin and R. R. Taintor (1987). L-arginine is required for the expression of activated macrophage effector mechanism causing selective metabolic inhibition in target cells,J. Immunol,138, 550–565.
M. W. Radomski, R. M. Palmer and S. Moncada (1990). Glucocorticoids inhibit the expression of an inducible, but not constitutive, nitric oxide synthase in vascular endothelial cells,Proc. Natl. Acad. Sci. USA 87, 10043–10047.
A. J. Farrell, D. R. Blake, R. M. J. Palmer et al. (1992). Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases,Ann. Rheum. Dis. 51, 1219–1222.
H. Sakurai, A. H. Khosak, M. Lin et al, (1995). Nitirc oxide production and inducible nitric oxide synthase expression in inflammatory arthritides,J. Clin. Invest. 96, 2357–2363.
M. Stefanovie-Raeie, K. Meyers, C. Mesehter et al. (1994). N-Monomethyl arginine, an inhibitor of nitric oxide syntase, suppresses the development of adjuvant arthritis in rats,Arthritis Rheum. 37, 1062–1069.
A. Wanchu, N. Agnihotri, S. D. Deodhar and N. K. Ganguly (1996). Plasma reactive nitrogen intermediate levels in patients with clinically active arheumatoid arthritis,Ind. J. Med. Res. 104, 263–268.
R. S. Dykhuzen, M. Copland, C. C. Smith et al. (1995). Plasma nitrate concentration and urinary nitrate excretion in patients with gastroenteritis,J. Infect. 31, 73–75.
F. C. Arnett, Y. S. M. Edwothy, D. A. Bloch et al. (1988). The American Rheumatism Association revised criteria for the classification of rheumatoid arthritis,Arthritis Rheum. 31, 315–324.
A. Wanchu, S. D. Deodhar, M. Sharma et al. (1997). Elevated levels of anti-proteus antibodies in patients with active rheumatoid arthritis,Ind. J. Med. Res. 105, 39–42.
L. C. Green, D. A. Wagner, J. Glogowski et al. (1982). Analysis of nitrate, nitrite and (15N) nitrate in biological fluids,Ann. Biochem. 126, 131–138.
T. R. Boyde and M. Rahamatullah (1980). Optimization of conditions for the colorimetric determination of citrolline, using diacetyl monoxime,Ann. Biochem. 107, 424–431.
H. Kaur and B. Halliweil (1994). Evidence for nitric oxide-mediated oxidative damage in chronic inflammation: nitrotyrosine in serum and synovial fluid from rheumatoid patients,FEBS Lett. 350, 9–12.
R. Wigand, J. Meyer, R. Busse and M. Hecker (1997). Increased serum NG- hydroxy-L-arginine in patients with rheumatoid arthritis and systemic lupus erythematosus as an index of increased nitric oxide synthase activity,Ann. Rheum. Dis. 56, 330–332.
D. A. Wagner, D. S. Schultz, W. M. Deen et al. (1983). Metabolic fate of an oral dose of 15N-labelled nitrate in humans: effect of diet supplementation with ascorbic acid,Cancer Res. 43, 1921–1925.
H. J. Hanselmann, L. Oppliger, B. A. Michel et al. (1994). Nitric oxide and proteoglycan biosynthesis by human articular chondrocytes in alginate culture,FEBS Lett. 352, 361–364.
S. H. Ralston, L. Ho, M. H. Helfrich et al. (1995). Nitric oxide: a cylokine induced regulator of bone resorption,J. Bone Miner. Res. 10, 1040–1049.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wanchu, A., Khullar, M., Sud, A. et al. Elevated urinary nitrite and citrulline levels in patients with rheumatoid arthritis. Inflammopharmacol 7, 155–161 (1999). https://doi.org/10.1007/BF02918387
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02918387