Role of nitric oxide in restitution of injured guinea pig gastric mucosa in vitro.
The role of nitric oxide (NO) in restitution was examined in intact sheets of in vitro guinea pig gastric mucosae after mucosal injury induced by exposure of the luminal surface to 1.25 M NaCl for 10 min. The recovery of transmucosal electrical resistance and [3H]mannitol flux after the injury were significantly greater at luminal pH (pH1) 7.0 than 3.0. The recovery was abolished by pretreatment with 1 mM NG-nitro-L-arginine methyl ester (L-NAME), only at pHL 3.0, an effect reversed by 1 mM L-arginine. Enhancement of the recovery by L-arginine at pHL 3.0 was abolished by 50 microM methylene blue (MB), an effect restored by 1 mM N6,2'-O-dibutyryl guanosine 3',5'-cyclic monophosphate (DBcGMP). In L-arginine- but not L-NAME-treated tissues, recovery was enhanced further by an increase in serosal [HCO3-] and was inhibited by 5% N-acetyl-L-cysteine in the luminal solution or by the removal of serosal HCO3-. Morphological examination showed the formation of a thick "mucoid cap" in L-arginine-but not L-NAME-treated tissues. These results suggest that, in the presence of luminal acid, endogenous NO contributes to restitution in injured gastric mucosa at least in part by facilitating the formation of the mucoid cap.
Yanaka
A
A
Department of Gastroenterology, University of Tsukuba, Ibaraki, Japan.
Muto
H
H
Fukutomi
H
H
Ito
S
S
Silen
W
W
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008751:Methylene Blue / Q000494:pharmacology; D008854:Microscopy, Electron; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D012462:Saline Solution, Hypertonic / Q000633:toxicity; D013237:Stereoisomerism; D013997:Time Factors; D019323:omega-N-Methylarginine
D001639:Bicarbonates; D012462:Saline Solution, Hypertonic; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; D008353:Mannitol; D001120:Arginine; D006152:Cyclic GMP; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester