title: The effect of consecutively larger doses of L-arginine on hepatic microcirculation and tissue oxygenation in hepatic steatosis.
abstract: BACKGROUND
  Impairment of hepatic microcirculation in fatty liver is thought to render it more susceptible to the effects of ischaemia-reperfusion injury as compared to non-fatty liver grafts. The present study aimed to investigate the effect of consecutively larger doses of L-arginine on the hepatic microcirculation and tissue oxygenation of fatty liver.
  
  
  METHODS
  Sprague-Dawley rats (200-250 g) were fed a liquid ethanol diet to induce hepatic steatosis or a normal diet for 6 weeks. Hepatic blood flow, microcirculation, tissue oxyhaemoglobin (HBO(2)) in response to consecutive intravenous bolus administrations of l-arginine (50 mg/kg, 100 mg/kg, 300 mg/kg and 500 mg/kg) or normal saline, were assessed.
  
  
  RESULTS
  Baseline hepatic arterial flows and hepatic microcirculation values were significantly lower in steatotic livers vs. control livers. L-arginine significantly improved hepatic arterial, portal venous blood flow, hepatic microcirculation and tissue oxygenation in both fatty and control livers.
  
  
  CONCLUSIONS
  The administration of NO in cumulatively larger doses is effective at improving hepatic blood flow, microcirculation and hepatic tissue oxygenation in steatotic liver and these results could form the basis of further work into using NO as a therapeutic tool to reclaim moderately steatotic grafts for use in liver transplantation.
authors: Hepatic Haemodynamic Laboratory, Academic Division of Surgical and Interventional Sciences, University College London, London NW3 2PF, UK. samiaijaz@hotmail.com
authors: Samia
authors: S
authors: Ijaz
authors: Marc C
authors: MC
authors: Winslet
authors: Alexander M
authors: AM
authors: Seifalian
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000378:metabolism / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008099:Liver / Q000098:blood supply* / Q000187:drug effects*; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011169:Portal Vein / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow
chemical_list: D009569:Nitric Oxide; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester