Serum, urinary, and salivary nitric oxide in rheumatoid arthritis: complexities of interpreting nitric oxide measures |
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Authors: | J Brice Weinberg Thomas Lang William E Wilkinson David S Pisetsky E William St Clair |
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Institution: | (1) Veterans Affairs Medical Center, 508 Fulton Street, Durham, NC 27705, USA;(2) Duke University Medical Center, 508 Fulton Street, Durham, NC 27705, USA;(3) University of Maryland School of Medicine, 10 South Pine Street, Baltimore, MD 21201, USA |
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Abstract: | Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and
other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary
nitrite and nitrate (NOx) in patients with RA and normal subjects, and we examined the relationships of these measures to
disease activity. Serum, urine, and NOx levels as well as renal creatinine, NOx clearance and fractional excretion rates were
compared in 25 RA patients and 20 age- and gender-matched healthy controls. Subjects were hospitalized for 3 days and placed
on a NOxrestricted diet. NOx was assayed using nitrate reductase and the Griess reagent. RA activity was assessed using standard
clinical and laboratory measures. While consuming a restricted diet for 3 days to eliminate the effects of oral intake of
NOx, 24 hour urinary NOx excretion decreased in both RA patients and healthy controls. Urine NOx levels at all time points
were not significantly different between RA patients and normal subjects. Serum NOx levels also decreased during the 3 days
of NOx restriction, but RA patients had higher serum NOx levels at all time points compared with the control group. Likewise,
serum NOx/creatinine ratios were higher in RA patients than in controls. Although basal salivary flow rate and tear flow were
lower in RA patients, salivary NOx levels did not differ between normal and RA subjects. While renal creatinine clearance
was not different between the two groups, we found that RA patients had lower renal NOx clearance and lower renal NOx fractional
excretion. After correction of p values for multiple comparisons, there were no significant relationships for the RA group between measures of disease activity
and the urinary NOx, serum NOx, or urinary NOx clearance. Despite interest in the use of NO as a marker of disease activity,
alterations in renal NOx clearance and fractional excretion in RA make it difficult to assess in vivo NO production even with strict dietary restriction of NOx intake. |
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