Role of inducible nitric oxide synthase in dextran sulphate sodium-induced colitis.
BACKGROUND
Different authors have postulated both toxic and protective effects for nitric oxide (NO) in the pathophysiology of active inflammation.


OBJECTIVE
To examine the role of NO, especially that produced by the inducible form of nitric oxide synthase (iNOS), by investigating the effects of NOS inhibitors and NO donors on inflammation in experimental acute colitis.


METHODS
Acute colitis was induced in rats by dextran sulphate sodium (DSS). White blood cell counts and levels of thiobarbituric acid reactants in the portal blood were determined, as were histological changes in the colonic mucosa. We then evaluated the effects of N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG) and an NO donor on DSS-induced changes in these inflammatory parameters.


CONCLUSIONS
Inhibition of NO production by either L-NAME or AG worsened DSS-induced inflammation, suggesting a protective role for NO in acute colitis. On the other hand, a NO donor also exaggerated DSS-induced inflammatory parameters, suggesting that acute colitis may be aggravated by either too much or too little NO. These results suggest that medical treatment of ulcerative colitis must aim for maintenance of appropriate NO levels in the intestinal mucosa.
Yoshida
Y
Y
The Second Department of Internal Medicine, National Defense Medical College, School of Medicine, Tokorozawa, Saitama, Japan.
Iwai
A
A
Itoh
K
K
Tanaka
M
M
Kato
S
S
Hokari
R
R
Miyahara
T
T
Koyama
H
H
Miura
S
S
Kobayashi
M
M
D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism*; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000009:adverse effects; D004790:Enzyme Induction; D006146:Guanidines / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006146:Guanidines; D009569:Nitric Oxide; D016264:Dextran Sulfate; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester