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 sh eets of in vitro guinea pig gastric mucosae after mucosal injury induc ed by exposure of the luminal surface to 1.25 M NaCl for 10 min. The r ecovery of transmucosal electrical resistance and [H-3]mannitol flux a fter the injury were significantly greater at luminal pH (pH(L)) 7.0 t han 3.0. The recovery was abolished by pretreatment with 1 mM N-G-nitr o-L-arginine methyl eater (L-NAME), only at pH(L) 3.0, an effect rever sed by 1 mM L-arginine. Enhancement of the recovery by L-arginine at p H(L) 3.0 was abolished by 50 mu M methylene blue (MB), an effect resto red by 1 mM N-6,2'-O-dibutyryl guanosine 3',5'-cyclic monophosphate (D BcGMP). In L-arginine- but not L-NAME-treated tissues, recovery was en hanced 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 se rosal HCO3-. Morphological examination showed the formation of a thick ''mucoid cap'' in L-arginine-but not L-NAME-treated tissues. These re sults suggest that, in the presence of luminal acid, endogenous NO con tributes to restitution in injured gastric mucosa at least in part by facilitating the formation of the mucoid cap.