title: Effect of neutropenia on gastric mucosal integrity and mucosal nitric oxide synthesis in the rat.
abstract: The present study examined the interaction between neutrophils and gastric mucosal nitric oxide (NO) synthesis in the regulation of gastric mucosal integrity in the rat. Male Sprague-Dawley rats were made neutropenic by intraperitoneal injections of methotrexate (MT; 2.5 mg/kg) or antineutrophil serum (ANS; 100 microliters). Control rats were treated with saline. Neutropenia was confirmed by circulating neutrophil counts and tissue myeloperoxidase activity. Neutropenic or control rats were given 2 ml of ethanol (EtOH; 40% w/v intragastrically). Neutropenic rats were less susceptible to EtOH-induced mucosal damage when compared to control rats. Mucosal NO synthesis was increased in neutropenic rats. EtOH instillation reduced NO synthase in control rats. However, in MT-treated rats the reduced NO synthase activity was not different from that observed in untreated control rats.
  
  
  CONCLUSIONS
  (1) EtOH-mediated gastric mucosal injury appears to be a neutrophil-mediated process. (2) Neutropenia results in an increase in mucosal NO synthesis. (3) MT treatment augments the degree of mucosal integrity. The increase in integrity is associated with a reduction in mucosal neutrophil infiltration as well as maintenance of NO synthase activity. ANS appears to influence mucosal integrity primarily by a reduction in circulating neutrophils.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Western Ontario, London, Canada.
authors.forename: B L
authors.initials: BL
authors.lastname: Tepperman
authors.forename: B L
authors.initials: BL
authors.lastname: Vozzolo
authors.forename: B D
authors.initials: BD
authors.lastname: Soper
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000009:adverse effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005756:Gastritis / Q000139:chemically induced / Q000378:metabolism; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008727:Methotrexate; D009503:Neutropenia / Q000209:etiology / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009569:Nitric Oxide; D000431:Ethanol; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D008727:Methotrexate