Inhibition of inducible nitric oxide synthase delays gastric ulcer healing in the rat.
We sought to clarify the role of nitric oxide (NO) generated from inducible NO synthase (iNOS) during healing of rat gastric ulcers. After gastric ulcers were induced by acetic acid, rats were treated with vehicle, N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), and dexamethasone (Dex) by gastric intubation twice a day for 3 days to 1 week. L-NAME significantly delayed healing compared with vehicle. AG and Dex significantly reduced ulcer size 3 days after ulcer induction but did not further reduce ulcer size 1 week after induction. iNOS expression was present in inflammatory cells, some epithelial cells, and in vascular smooth muscle in the regenerating mucosa of the vehicle-treated group. However, the number of iNOS-positive inflammatory cells increased in the AG- and L-NAME-treated groups. AG and L-NAME significantly increased the number of inflammatory cells with endogenous peroxidase and significantly reduced the number of apoptotic inflammatory cells compared with vehicle. In conclusion, inhibition of iNOS increases the number of inflammatory cells in the ulcer margin and delays ulcer healing. These observations suggest that NO generated from iNOS not only participates in ulcer formation but also plays a beneficial role in ulcer healing, in part by the exclusion of iNOS-positive inflammatory cells from the regenerating mucosa.
Akiba
Y
Y
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Nakamura
M
M
Mori
M
M
Suzuki
H
H
Oda
M
M
Kimura
H
H
Miura
S
S
Tsuchiya
M
M
Ishii
H
H
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006146:Guanidines / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000378:metabolism* / Q000473:pathology
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester