Potential role of nitric oxide in a model of chronic colitis in rhesus macaques.
OBJECTIVE
Excess nitric oxide formation, via the inducible NO synthase isoform, has been implicated in the pathogenesis of experimental and clinical inflammatory bowel disease. The aim of this study was to assess the site, enzyme source, and magnitude of NO production in juvenile rhesus macaques with idiopathic colitis.


METHODS
NO production was assessed systemically from plasma and urine levels of reactive nitrogen intermediates and locally by the formation of [3H]citrulline from [3H]arginine and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry. Inducible NO synthase gene expression was assessed by reverse-transcription polymerase chain reaction.


RESULTS
Plasma and urine levels of reactive nitrogen intermediates were greater in colitic animals than in control monkeys by 13- and 5-fold, respectively. NADPH diaphorase activity in normal animals was confined to the myenteric plexus. In colitis, staining was also apparent in crypt abscesses and superficial epithelial and mucosal bands. Gene expression for inducible NO synthase was only found in colitic specimens. Colonic [3H]citrulline formation was markedly elevated in colitic specimens, and the inducible isoform accounted for 58% of total activity.


CONCLUSIONS
It is proposed that excess NO, formed via the inducible form of NO synthase, contributes to the mucosal inflammation and symptoms of this idiopathic colitis model.
Ribbons
K A
KA
Department of Pediatrics, Louisiana State University Medical Center, New Orleans.
Zhang
X J
XJ
Thompson
J H
JH
Greenberg
S S
SS
Moore
W M
WM
Kornmeier
C M
CM
Currie
M G
MG
Lerche
N
N
Blanchard
J
J
Clark
D A
DA
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002908:Chronic Disease; D003092:Colitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000378:metabolism; D008253:Macaca mulatta; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000097:blood; D012313:RNA / Q000378:metabolism; D014018:Tissue Distribution
D015335:Molecular Probes; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D012313:RNA; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase