ADAPTIVE CYTOPROTECTION OF THE RAT DUODENUM IS NOT DEPENDENT ON NITRIC OXIDE-INDUCED CHANGES IN BLOOD-FLOW

Mild irritation of the rat duodenum enhances mucosal resistance to aci d via a prostaglandin-mediated mechanism. Prostaglandins increase muco sal blood flow, but it is not known whether such changes in blood flow significantly contribute to adaptive cytoprotection. We induced blood flow changes by manipulating the arginine-nitric oxide pathway, which is independent from prostaglandin synthesis, and determined the resul ting effects on the cytoprotective response. In anesthetized rats, we tested the effects of intraduodenal infusion of mild acid on duodenal blood flow and on the prevention of mucosal damage by subsequent stron g acid in control, indomethacin-pretreated, and N(G)-nitro-L-arginine- pretreated rats (N(G)-nitro-L-arginine inhibits the nitric oxide synth ase). Additional experiments tested the effects of the prostaglandin a nalogue 16,16-dimethyl-prostaglandin (PG) E2 or sodium nitroprusside ( nitric oxide donor) on duodenal blood flow and on mucosal protection a gainst acid. Exposure of the duodenal mucosa to mild acid increased du odenal blood flow and mucosal resistance to acid. Instillation of 16,1 6-dimethyl-PGE2 also increased blood flow and mucosal resistance to ac id. However, sodium nitroprusside increased blood flow without increas ing mucosal resistance to acid, and N(G)-nitro-L-arginine inhibited th e change in blood flow induced by acid while preserving the adaptive c ytoprotection phenomenon intact. In conclusion, adaptive cytoprotectio n of the duodenal mucosa appears to be independent of changes in blood flow.