title: Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat.
abstract: 1. The interactions between nitric oxide (NO), prostacyclin and sensory neuropeptides in the maintenance of gastric mucosal integrity have been investigated in the anaesthetized rat. 2. Administration of either NG-monomethyl-L-arginine (L-NMMA) to inhibit endothelium-derived NO formation, indomethacin to inhibit prostanoid biosynthesis or chronic capsaicin pretreatment to deplete sensory neuropeptides, did not induce acute mucosal injury. 3. In capsaicin-pretreated rats, however, L-NMMA (12.5-100 mg kg-1 i.v.) dose-dependently induced acute mucosal damage, characterized as vasocongestion and haemorrhagic necrosis. The enatiomer D-NMMA (100 mg kg-1 i.v.) did not induce any detectable mucosal damage. 4. This mucosal injury induced by L-NMMA was inhibited by concurrent administration of L-arginine (300 mg kg-1 i.v.). 5. In indomethacin (5 mg kg-1 i.v.)-pretreated rats, L-NMMA also induced mucosal damage. Furthermore, following indomethacin administration in capsaicin-pretreated rats, L-NMMA induced widespread, severe haemorrhagic necrotic damage. 6. These findings suggest a role for endogenous NO formed from L-arginine, acting in concert with prostacyclin and sensory neuropeptides, in the modulation of gastric mucosal integrity.
authors.affiliation: Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent.
authors.forename: B J
authors.initials: BJ
authors.lastname: Whittle
authors.forename: J
authors.initials: J
authors.lastname: Lopez-Belmonte
authors.forename: S
authors.initials: S
authors.lastname: Moncada
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced; D019323:omega-N-Methylarginine
chemical_list: D009479:Neuropeptides; D011453:Prostaglandins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D011464:Epoprostenol; D002211:Capsaicin; D007213:Indomethacin