MULTIPLE MEDIATORS AND MECHANISMS ARE INVOLVED IN THE ADAPTIVE CYTOPROTECTION PROVIDED BY CERTAIN MILD IRRITANTS

We investigated the participation of prostaglandins (PG) and nitric ox ide (NO) in adaptive cytoprotection using 0.6 N HCl-induced gastric le sions in the rat stomach. Indomethacin reversed the protective effect of 0.2 N HCl more strongly than that of 0.35 N HCl, both of which mark edly inhibited HCl ulcer. N(G)-Nitro-L-arginine (L-NNA) did not affect the protective effect afforded by either 0.2 N HCl or 0.35 N HCl. Com bined pretreatment with indomethacin and L-NNA did not diminish the pr otective action induced by 0.35 N HCl, but almost completely abolished the indomethacin-resistant protection afforded by 0.1 N NaOH. Acid mi ld irritant increased the gastric fluid volume concentration-dependent ly, whereas alkaline mild irritant had little or no effect on the volu me. These results suggest that: 1) The mediators involved in adaptive cytoprotect ion afforded by 0.1 N NaOH may be fully ascribed to PG and NO; 2) PG is a maj or mediator in the protection induced by 0.2 N HCl ; 3) In the case of 0.35 N HCl, the mediators remain to be determined since increased gastric fluid volume could contribute to the protectio n through dilution. These findings thus may indicate that multiple med iators and mechanisms are implicated in adaptive cytoprotection.