title: Role of nitric oxide in maintaining vascular integrity in endotoxin-induced acute intestinal damage in the rat.
abstract: 1. The role of endogenous nitric oxide (NO) in maintaining intestinal vascular integrity following acute endotoxin (E. coli. lipopolysaccharide) challenge was investigated in the anaesthetized rat by use of NG-monomethyl-L-arginine (L-NMMA), a selective inhibitor of NO synthesis. 2. L-NMMA (10-50 mg kg-1, i.v.) pretreatment enhanced both the macroscopic and histological intestinal damage and the increases in vascular permeability, measured as the leakage of [125I]-labelled human serum albumen, induced after 15 min by endotoxin (50 mg kg-1, i.v.). 3. The effects of L-NMMA (50 mg kg-1, i.v.) were enantiomer specific, as D-NMMA had no effect. Furthermore, these effects were reversed by L-arginine (300 mg kg-1, i.v.), the precursor of NO synthesis but not by D-arginine (300 mg kg-1, i.v.). 4. L-NMMA (10-50 mg kg-1, i.v.) increased mean systemic arterial blood pressure but this does not appear to be the mechanism by which endotoxin-induced intestinal damage was enhanced, since similar systemic pressor responses induced by phenylephrine (10 micrograms kg-1 min-1, i.v.), had no such effect. 5. The results suggest that synthesis of NO from L-arginine has a role in maintaining the microvascular integrity of the intestinal mucosa following acute endotoxin challenge.
authors.affiliation: Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent.
authors.forename: I R
authors.initials: IR
authors.lastname: Hutcheson
authors.forename: B J
authors.initials: BJ
authors.lastname: Whittle
authors.forename: N K
authors.initials: NK
authors.lastname: Boughton-Smith
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001772:Blood Cell Count; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity*; D006470:Hemorrhage / Q000139:chemically induced / Q000503:physiopathology; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007457:Iodine Radioisotopes; D007583:Jejunum / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019323:omega-N-Methylarginine
chemical_list: D004731:Endotoxins; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine