title: Monochloramine impairs mucosal blood flow response and healing of gastric lesions in rats: relation to capsaicin-sensitive sensory neurons.
abstract: OBJECTIVE
  We examined the effects of monochloramine (NH2Cl) on the gastric mucosal blood flow (GMBF) response and the healing of ethanol-induced gastric lesions in rats.
  
  
  METHODS
  Rats fasted for 18 h were given the 99% ethanol p.o. for induction of gastric lesions, and were fed normally from 1 h later onwards. Monochloramine, at non-ulcerogenic doses (5 to approximately 20 mmol/L), was given p.o. twice daily for 7 days, starting 2 h after ethanol treatment.
  
  
  RESULTS
  Gastric lesions caused by ethanol healed almost completely within 7 days with re-epithelialization. The repeated administration of NH2Cl significantly delayed the healing of ethanol-induced gastric lesions in a dose-dependent manner. The damaged mucosa showed a marked rise in H+ permeability, resulting in luminal acid loss, but this process was accompanied by an increase of mucosal blood flow. Monochloramine did not affect the increased mucosal H+ permeability observed in the stomach after damage by ethanol, but significantly inhibited the mucosal hyperemic response associated with luminal acid loss. Prior exposure of the mucosa to NH2Cl (20 mmol/L) did not affect the gastric hyperemic response caused by mucosal application of misoprostol (a prostaglandin E1 derivative) or NOR-3 (a nitric oxide donor), but totally attenuated the increase of GMBF in response to intragastric capsaicin. Impaired healing and GMBF responses were also observed in rats following chemical ablation of capsaicin-sensitive sensory neurons.
  
  
  CONCLUSIONS
  These results suggest that NH2Cl impaired the healing of acute gastric mucosal lesions at low concentrations, and this action may be attributable, at least partly, to the impairment of gastric hyperemic response caused by the dysfunction of capsaicin-sensitive sensory neurons.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Japan. takeuchi@mb.kyoto-phu.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: H
authors.initials: H
authors.lastname: Araki
authors.forename: H
authors.initials: H
authors.lastname: Nishiwaki
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002700:Chloramines / Q000494:pharmacology*; D003714:Denervation; D004351:Drug Resistance; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply* / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013270:Stomach / Q000187:drug effects / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D013272:Stomach Diseases / Q000503:physiopathology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D002700:Chloramines; D000431:Ethanol; D006859:Hydrogen; C030816:chloramine; D002211:Capsaicin