Expression of NOS II and its role in experimental small bowel ulceration in rats.
BACKGROUND
Overproduction of nitric oxide (NO) has been implicated in the pathogenesis of experimental and clinical inflammatory bowel disease (IBD).


METHODS
We observed the expression and localization of inducible NO synthase (NOS-II) in small intestinal ulceration induced by indomethacin in rats. The role of NO was investigated by using NO synthase inhibitors.


RESULTS
The small intestine was affected by longitudinal ulcers after indomethacin administration and ulceration was associated with distinctive expression of NOS-II protein and mRNA. The amount of its expression was found to correlate with the extent of inflammation. Histologically, both immunohistochemistry and in situ hybridization revealed a similar localization of NOS-II to inflammatory and epithelial cells. The possible amelioration of the inflammation was modulated by aminoguanidine (AG) and NG-nitro-L-arginine methyl ester (L-NAME) treatment for 10 days. Both AG and L-NAME attenuated intestinal myeloperoxidase activity and gross inflammation, only AG was found to decrease intestinal permeability with a significant amelioration of body weight loss.


CONCLUSIONS
These findings indicate that NO derived mainly from inflammatory cells may play an important role in the pathophysiology of intestinal ulceration and offer the potential for future treatment directed at blocking neutrophils recruitment and NO overproduction in IBD.
Chen
K
K
Department of Pediatric Surgery, Osaka University Medical School, Japan.
Hirota
S
S
Wasa
M
M
Okada
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000633:toxicity; D015212:Inflammatory Bowel Diseases / Q000209:etiology; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010437:Peptic Ulcer / Q000201:enzymology* / Q000209:etiology* / Q000235:genetics; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; D009195:Peroxidase; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin