Elevated nitric oxide production in rheumatoid arthritis: Detection using the fasting urinary nitrate:creatinine ratio

Abstract

Objective. To develop a simple method for assessing endogenous nitric oxide (NO) production applicable to routine clinical practice in rheumatology. Methods. NO production was assessed in patients with rheumatoid arthritis (RA) as serum nitrate levels and as the urinary nitrate:creatinine ratio in morning samples of urine following an overnight fast. The influence of dietary intake of nitrate on these measurements was investigated in healthy volunteers. The clinical value of the urinary nitrate:creatinine ratio was validated in patients with infectious gastroenteritis, in whom its production is known to be increased. Results. Urinary nitrate:creatinine ratios were significantly elevated in patients with RA (average 3-fold elevation over controls; P < 0.005) or infectious gastroenteritis (average 10-fold elevation, P < 0.001). Serum nitrate was significantly elevated only in patients with infectious gastroenteritis (P < 0.001). Dietary intake of nitrate had no significant influence on the fasting morning urinary nitrate:creatinine ratio in the healthy volunteers, showing that this parameter is a useful indicator of endogenous NO production. Conclusion. We have developed a simple procedure for evaluating endogenous NO production that is readily applicable to routine clinical practice. Assessment of NO production will help in our understanding of its role in inflammatory conditions such as RA.