title: Highly selective inhibition of inducible nitric oxide synthase ameliorates experimental acute pancreatitis.
abstract: OBJECTIVE
  Inducible nitric oxide synthase (iNOS) activity is increased in experimental acute pancreatitis. The aim of this study was to evaluate treatment with the selective iNOS inhibitors AR-C (AR-C102222AA) and L-NIL (L-N6-(1-iminoethyl)-lysine) in experimental acute pancreatitis.
  
  
  METHODS
  Acute pancreatitis was induced in anesthetized Australian possums by topical administration of carbachol on the sphincter of Oddi. AR-C treatment was 2 intravenous infusions (2.5 micromol/kg over 15 minutes) at 2 and 4 hours after acute pancreatitis induction. L-NIL treatment was an intraarterial infusion (1 mg/kg/h) from 2 hours after acute pancreatitis induction. At 8 hours, pancreatic tissue was harvested and inflammation assessed (histologic score). Blood samples were collected for plasma amylase, lipase, and amino acid levels. Blood pressure, central venous pressure, supplementary fluids, and urine output were monitored.
  
  
  RESULTS
  Treatment with AR-C or L-NIL reduced the plasma levels of amylase and the volume of supplementary fluids and improved the histological score (all P < 0.05). In animals with acute pancreatitis, plasma arginine levels were reduced (P < 0.05), while citrulline and ornithine levels increased (P < 0.05), consistent with increased nitric oxide production. Treatment with AR-C ameliorated the reduced arginine level.
  
  
  CONCLUSIONS
  Treatment with AR-C or L-NIL, commencing 2 hours after the induction of acute pancreatitis, has significant and beneficial effects in experimental acute pancreatitis in Australian possums.
authors.affiliation: Department of Biomedicine and Surgery, University Hospital of Linkoping, Linkoping, Sweden. per.sandstrom@lio.se
authors.forename: Per
authors.initials: P
authors.lastname: Sandstrom
authors.forename: Mark E
authors.initials: ME
authors.lastname: Brooke-Smith
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Thomas
authors.forename: Marlene B
authors.initials: MB
authors.lastname: Grivell
authors.forename: Gino T P
authors.initials: GT
authors.lastname: Saccone
authors.forename: James
authors.initials: J
authors.lastname: Toouli
authors.forename: Joar
authors.initials: J
authors.lastname: Svanvik
mesh_terms: D000208:Acute Disease; D000596:Amino Acids / Q000097:blood; D000681:Amylases / Q000097:blood; D000818:Animals; D002496:Central Venous Pressure; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006400:Hematocrit; D008049:Lipase / Q000097:blood; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010195:Pancreatitis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology*; D048330:Trichosurus; D014882:Water-Electrolyte Balance
chemical_list: C489944:AR C102222AA; D000596:Amino Acids; D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D011799:Quinazolines; D052247:Nitric Oxide Synthase Type II; D008049:Lipase; D000681:Amylases; D008239:Lysine