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 acid via a prostaglandin-mediated mechanism. Prostaglandins increase mucosal 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 resulting 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 strong acid in control, indomethacin-pretreated, and NG-nitro-L-arginine-pretreated rats (NG-nitro-L-arginine inhibits the nitric oxide synthase). Additional experiments tested the effects of the prostaglandin analogue 16,16-dimethyl-prostaglandin (PG) E2 or sodium nitroprusside (nitric oxide donor) on duodenal blood flow and on mucosal protection against acid. Exposure of the duodenal mucosa to mild acid increased duodenal blood flow and mucosal resistance to acid. Instillation of 16,16-dimethyl-PGE2 also increased blood flow and mucosal resistance to acid. However, sodium nitroprusside increased blood flow without increasing mucosal resistance to acid, and NG-nitro-L-arginine inhibited the change in blood flow induced by acid while preserving the adaptive cytoprotection phenomenon intact. In conclusion, adaptive cytoprotection of the duodenal mucosa appears to be independent of changes in blood flow.
Lugea
A
A
Digestive System Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, Spain.
Salas
A
A
Guarner
F
F
Malagelada
J R
JR
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002588:Cesium Radioisotopes; D004386:Duodenum / Q000098:blood supply / Q000473:pathology / Q000502:physiology*; D006851:Hydrochloric Acid / Q000633:toxicity; D007413:Intestinal Mucosa / Q000098:blood supply / Q000473:pathology / Q000502:physiology*; D008297:Male; D008863:Microspheres; D008871:Microvilli / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
D002588:Cesium Radioisotopes; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D015064:16,16-Dimethylprostaglandin E2; D006851:Hydrochloric Acid