Highly selective inhibition of inducible nitric oxide synthase ameliorates experimental acute pancreatitis

© 2005 Lippincott Williams & Wilkins, Inc.ObjectivesInducible 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.MethodsAcute 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.ResultsTreatment 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 ConclusionsTreatment 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.Per Sandstrom, Mark E. Brooke-Smith, Anthony C. Thomas, Marlene B. Grivell, Gino T. P. Saccone, James Toouli, Joar Svanvikhttp://www.ncbi.nlm.nih.gov/pubmed/1563269