title: Nitric oxide synthase distribution and expression with ischemic preconditioning of the rat liver.
abstract: This study was undertaken to identify nitric oxide synthase (NOS) isoforms responsible for the generation of cytoprotective NO during liver ischemic preconditioning (IPC). Sprague-Dawley rats were subjected to 45 min lobar ischemia followed by 2 h reperfusion. L-arginine or Nomega-nitro-L-arginine methyl ester (L-NAME) was administered to stimulate or block NO synthesis. Study groups (n=6) had 1) sham laparotomy, 2) ischemia reperfusion (IR), 3) IPC with 5 min ischemia and 10 min reperfusion before IR, 4) L-arginine before IR, or 5) L-NAME + IPC before IR. Liver function tests, nitrite + nitrate (NOx) and plasma amino acids were analyzed. The endothelial cell and inducible isoforms of NOS (eNOS and iNOS) were identified using immunohistochemistry and Western blotting. Both IPC and L-arginine treatment increased NOx (P<0.05) and improved serum liver enzymes (P<0.05) when compared with IR. These effects were prevented by L-NAME. Hepatic vein NOx was significantly higher than circulating NOx. iNOS expression was absent within the groups. The preconditioned livers were associated with up-regulation of eNOS expression and also increased L-arginine levels. The effects of L-arginine administration were similar to those evident following IPC. Thus, cytoprotective NO generation during IPC of the liver was a result of increased eNOS expression and increased L-arginine substrate availability.
authors.affiliation: Academic Division of Surgical and Interventional Sciences, University College London, London, UK.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Koti
authors.forename: Janice
authors.initials: J
authors.lastname: Tsui
authors.forename: Edgar
authors.initials: E
authors.lastname: Lobos
authors.forename: Wenxuan
authors.initials: W
authors.lastname: Yang
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Seifalian
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davidson
mesh_terms: D000596:Amino Acids / Q000097:blood; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D019610:Cytoprotection; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis*; D052250:Nitric Oxide Synthase Type III / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology
chemical_list: D000596:Amino Acids; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester