Abstract
OBJECTIVES--To determine daily production of nitric oxide (NO) measured as urinary nitrate excretion, and the effect of prednisolone in patients with rheumatoid arthritis (RA). METHODS--Twenty four hour urinary nitrate was measured by gas chromatography in 10 patients with RA, before and two to four weeks after commencement of prednisolone 0.5 mg/kg body weight, and in 18 healthy controls. RESULTS--Before the start of prednisolone treatment the urinary nitrate excretion in patients with RA was 2.7-fold greater (p < 0.001) than that in healthy volunteers. After prednisolone it decreased significantly, by 28%, at which time inflammatory activity (as indicated by C reactive protein, erythrocyte sedimentation rate, joint count, and early morning stiffness) was also reduced considerably. Despite this decrease, the urinary nitrate excretion in patients with RA remained twice that in the control group (p < 0.05). CONCLUSIONS--Our data suggest that the endogenous production of NO is enhanced in patients with RA. Furthermore, the results indicate that, in parallel with suppression of inflammation, this increased NO synthesis could be reduced by prednisolone treatment.
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- Arend W. P., Dayer J. M. Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum. 1990 Mar;33(3):305–315. doi: 10.1002/art.1780330302. [DOI] [PubMed] [Google Scholar]
- Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
- Billiar T. R., Curran R. D., Harbrecht B. G., Stuehr D. J., Demetris A. J., Simmons R. L. Modulation of nitrogen oxide synthesis in vivo: NG-monomethyl-L-arginine inhibits endotoxin-induced nitrate/nitrate biosynthesis while promoting hepatic damage. J Leukoc Biol. 1990 Dec;48(6):565–569. doi: 10.1002/jlb.48.6.565. [DOI] [PubMed] [Google Scholar]
- Bode-Böger S. M., Böger R. H., Creutzig A., Tsikas D., Gutzki F. M., Alexander K., Frölich J. C. L-arginine infusion decreases peripheral arterial resistance and inhibits platelet aggregation in healthy subjects. Clin Sci (Lond) 1994 Sep;87(3):303–310. doi: 10.1042/cs0870303. [DOI] [PubMed] [Google Scholar]
- Di Rosa M., Radomski M., Carnuccio R., Moncada S. Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1246–1252. doi: 10.1016/0006-291x(90)91583-e. [DOI] [PubMed] [Google Scholar]
- Farrell A. J., Blake D. R., Palmer R. M., Moncada S. Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis. 1992 Nov;51(11):1219–1222. doi: 10.1136/ard.51.11.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fuchs H. A., Brooks R. H., Callahan L. F., Pincus T. A simplified twenty-eight-joint quantitative articular index in rheumatoid arthritis. Arthritis Rheum. 1989 May;32(5):531–537. doi: 10.1002/anr.1780320504. [DOI] [PubMed] [Google Scholar]
- Förstermann U., Closs E. I., Pollock J. S., Nakane M., Schwarz P., Gath I., Kleinert H. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension. 1994 Jun;23(6 Pt 2):1121–1131. doi: 10.1161/01.hyp.23.6.1121. [DOI] [PubMed] [Google Scholar]
- Garthwaite J., Charles S. L., Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature. 1988 Nov 24;336(6197):385–388. doi: 10.1038/336385a0. [DOI] [PubMed] [Google Scholar]
- Granger D. L., Hibbs J. B., Jr, Broadnax L. M. Urinary nitrate excretion in relation to murine macrophage activation. Influence of dietary L-arginine and oral NG-monomethyl-L-arginine. J Immunol. 1991 Feb 15;146(4):1294–1302. [PubMed] [Google Scholar]
- Green L. C., Ruiz de Luzuriaga K., Wagner D. A., Rand W., Istfan N., Young V. R., Tannenbaum S. R. Nitrate biosynthesis in man. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7764–7768. doi: 10.1073/pnas.78.12.7764. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gutzki F. M., Tsikas D., Alheid U., Frölich J. C. Determination of endothelium-derived nitrite/nitrate by gas chromatography/tandem mass spectrometry using (15N)NaNO2 as internal standard. Biol Mass Spectrom. 1992 Feb;21(2):97–102. doi: 10.1002/bms.1200210207. [DOI] [PubMed] [Google Scholar]
- Hunt N. C., Goldin R. D. Nitric oxide production by monocytes in alcoholic liver disease. J Hepatol. 1992 Mar;14(2-3):146–150. doi: 10.1016/0168-8278(92)90150-n. [DOI] [PubMed] [Google Scholar]
- Ialenti A., Moncada S., Di Rosa M. Modulation of adjuvant arthritis by endogenous nitric oxide. Br J Pharmacol. 1993 Oct;110(2):701–706. doi: 10.1111/j.1476-5381.1993.tb13868.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ignarro L. J. Signal transduction mechanisms involving nitric oxide. Biochem Pharmacol. 1991 Feb 15;41(4):485–490. doi: 10.1016/0006-2952(91)90618-f. [DOI] [PubMed] [Google Scholar]
- Kaur H., Halliwell B. Evidence for nitric oxide-mediated oxidative damage in chronic inflammation. Nitrotyrosine in serum and synovial fluid from rheumatoid patients. FEBS Lett. 1994 Aug 15;350(1):9–12. doi: 10.1016/0014-5793(94)00722-5. [DOI] [PubMed] [Google Scholar]
- Kilbourn R. G., Belloni P. Endothelial cell production of nitrogen oxides in response to interferon gamma in combination with tumor necrosis factor, interleukin-1, or endotoxin. J Natl Cancer Inst. 1990 May 2;82(9):772–776. doi: 10.1093/jnci/82.9.772. [DOI] [PubMed] [Google Scholar]
- Kubes P., Suzuki M., Granger D. N. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651–4655. doi: 10.1073/pnas.88.11.4651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCartney-Francis N., Allen J. B., Mizel D. E., Albina J. E., Xie Q. W., Nathan C. F., Wahl S. M. Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med. 1993 Aug 1;178(2):749–754. doi: 10.1084/jem.178.2.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moncada S., Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec 30;329(27):2002–2012. doi: 10.1056/NEJM199312303292706. [DOI] [PubMed] [Google Scholar]
- Moncada S. The 1991 Ulf von Euler Lecture. The L-arginine: nitric oxide pathway. Acta Physiol Scand. 1992 Jul;145(3):201–227. doi: 10.1111/j.1748-1716.1992.tb09359.x. [DOI] [PubMed] [Google Scholar]
- Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
- Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Hickery M. S., Charles I. G., Moncada S., Bayliss M. T. Induction of nitric oxide synthase in human chondrocytes. Biochem Biophys Res Commun. 1993 May 28;193(1):398–405. doi: 10.1006/bbrc.1993.1637. [DOI] [PubMed] [Google Scholar]
- Radomski M. W., Palmer R. M., Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol. 1987 Sep;92(1):181–187. doi: 10.1111/j.1476-5381.1987.tb11310.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stefanovic-Racic M., Meyers K., Meschter C., Coffey J. W., Hoffman R. A., Evans C. H. N-monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats. Arthritis Rheum. 1994 Jul;37(7):1062–1069. doi: 10.1002/art.1780370712. [DOI] [PubMed] [Google Scholar]
- Stefanovic-Racic M., Stadler J., Evans C. H. Nitric oxide and arthritis. Arthritis Rheum. 1993 Aug;36(8):1036–1044. doi: 10.1002/art.1780360803. [DOI] [PubMed] [Google Scholar]
- Stichtenoth D. O., Gutzki F. M., Tsikas D., Selve N., Bode-Böger S. M., Böger R. H., Frölich J. C. Increased urinary nitrate excretion in rats with adjuvant arthritis. Ann Rheum Dis. 1994 Aug;53(8):547–549. doi: 10.1136/ard.53.8.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suzuki H., Ikenaga H., Hishikawa K., Nakaki T., Kato R., Saruta T. Increases in NO2-/NO3- excretion in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure. Clin Sci (Lond) 1992 Jun;82(6):631–634. doi: 10.1042/cs0820631. [DOI] [PubMed] [Google Scholar]
- Wennmalm A., Benthin G., Petersson A. S. Dependence of the metabolism of nitric oxide (NO) in healthy human whole blood on the oxygenation of its red cell haemoglobin. Br J Pharmacol. 1992 Jul;106(3):507–508. doi: 10.1111/j.1476-5381.1992.tb14365.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Vliet A., O'Neill C. A., Halliwell B., Cross C. E., Kaur H. Aromatic hydroxylation and nitration of phenylalanine and tyrosine by peroxynitrite. Evidence for hydroxyl radical production from peroxynitrite. FEBS Lett. 1994 Feb 14;339(1-2):89–92. doi: 10.1016/0014-5793(94)80391-9. [DOI] [PubMed] [Google Scholar]