Effects of chronic superficial injury on the rat gastric mucosa.

The effects of chronic superficial injury on the stomach were studied in rats dosed with a mild irritant (2 mol/L NaCl intragastrically) every 48 hours for 1 month followed by 1-month recovery. A single exposure to this mild irritant induced gross protection against 6 mol/L NaCl for 1 but not 2 days. Leukotriene C4 (LTC4) levels increased slightly. Prostaglandin E2 (PGE2) concentration was unchanged. After 2-week dosing, protection was concomitant with markedly elevated PGE2 concentration. LTC4 values remained unchanged. Superficial epithelial cells were more resistant to damage. After 4-week dosing, protection occurred at 1 but not 2 days after the dose with an inverse correlation of PGE2. LTC4 concentration increased significantly at both times. Chronic injury for 1 month did not alter rapid epithelial restitution or PGE2 and LTC4 released 15 minutes after challenge with 6 mol/L NaCl. The recovery period showed loss of protection. PGE2 values returned to control levels but LTC4 values remained slightly elevated. It is concluded that short- or long-term (4-week) "adaptive cytoprotection" is not mediated by endogenous PGE2. Only extremely high levels of LTC4 correlated with loss of protection. The role of the more resistant superficial epithelium remains unknown.