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 (HbO2) 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 HbO2 and Cyt Ox were improved both in fatty and control livers following l-arginine, while l-NAME resulted in decreased HbO2 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.
Ijaz
Samia
S
Hepatic Hemodynamic Laboratory, Academic Division of Surgical and Interventional Sciences, University College London, London NW3 2PF, UK.
Yang
Wenxuan
W
Winslet
Marc C
MC
Seifalian
Alexander M
AM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005234:Fatty Liver / Q000473:pathology*; D006454:Hemoglobins / Q000737:chemistry; D050356:Lipid Metabolism; D008055:Lipids; D008099:Liver / Q000098:blood supply* / Q000378:metabolism*; D008297:Male; D008833:Microcirculation; D019331:NG-Nitroarginine Methyl Ester / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D006454:Hemoglobins; D008055:Lipids; D009566:Nitrates; D009573:Nitrites; D010108:Oxyhemoglobins; D014280:Triglycerides; D009569:Nitric Oxide; D001120:Arginine; D002784:Cholesterol; D003576:Electron Transport Complex IV; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester