The role of nitric oxide in the modulation of hepatic microcirculation and tissue oxygenation in an experimental model of hepatic steatosis

Background: Impairment of hepatic microcirculation in fatty liver has been assumed to reduce tolerance of the liver against ischemia-reperfusion injury. The present study was aimed to investigate the role of nitric oxide (NO) in the regulation of hepatic microcirculation and tissue oxygenation in hepatic steatosis. Methods: Sprague-Dawley rats (200-250 g) were fed a 2% cholesterol diet (n = 12) to induce hepatic steatosis or normal diet (n = 12) served as controls for 12 weeks. Hepatic blood flow, microcirculation, tissue oxyhemoglobin (HbO(2)) and cytochrome c oxidase radox status (Cyt Ox) in response to intravenous bolus administrations of L-arginine (300 mg/kg) or L-NAME (20 mg/kg) were assessed. Results: Animals which developed moderate hepatic steatosis showed significant increase in tissue level of total lipids. Portal blood flow and hepatic microcirculation were significantly reduced as compared to controls (5.7 +/- 0.9 vs. 9.7 +/- 0.9 ml/min, P = 0.003 and 114.5 +/- 9.5 vs. 167.3 +/- 10.0 flux unit, P = 0.003). L-Arginine improved hepatic arterial and portal blood flows as well as microcirculation in fatty livers (P < 0.05), while L-NAME significantly worsened these parameters (P < 0.05). Hepatic tissue HbO(2) and Cyt Ox were improved both in fatty and control livers following L-arginine, while L-NAME resulted in decreased HbO(2) and Cyt Ox although a transit increase in tissue oxygenation was observed in fatty livers. Conclusions: NO is involved in the modulation of hepatic microcirculatory perfusion and oxygenation in cholesterol-induced hepatic steatosis. NO metabolisms may be regulated as a potential therapeutic strategy for impaired microcirculation in hepatic steatosis. (c) 2005 Elsevier Inc. All rights reserved.