Role of nitric oxide in oxygen transport in rat liver sinusoids during endotoxemia

Abstract

tor, tumor necrosis factor, and other cytokines. 4 All of these To evaluate the role of nitric oxide (NO) in hepatic micromediators may be involved in the pathogenesis of liver injury, circulation and liver injury during endotoxemia, we studied probably initiated by microvascular disturbance caused by O 2 transport in the hepatic microcirculation of endotoxinleukocyte adhesion to endothelial cells in the hepatic sinuinfused rats. Rats were continuously infused with Escherichia soids. [5][6][7] Nitric oxide (NO) also increases during endotoxcoli lipopolysaccharide (LPS) (0.8 mg/kg/h) for 7 hours. LPS emia 8,9 and sepsis, 10 produced by Kupffer cells, macrophages, increased the plasma levels of NO 0 2 / NO 0 3 and aspartate hepatocytes, and sinusoidal endothelial cells. 9 Overproductransaminase (AST), and decreased the bile flow rate and tion of NO plays a toxic role in septic shock. 11 Peroxynitrite hepatic adenosine triphosphate (ATP) level. Hepatic microcirgenerated from superoxide and NO may be involved in sevculation was evaluated by two methods: reflectance spectroeral types of tissue injury. 12,13 On the contrary, NO attenuates photometry showed a decrease in the oxygenation of hemoglohepatic injury during endotoxemia. 14-17 Thus, the roles of bin (Hb) in the liver, and dual-spot microspectroscopy NO in endotoxemia are controversial. Nishida et al. recently indicated that LPS administration decreased blood velocity, reported that inhibition of NO synthesis in endotoxemia led the oxygenation of Hb, and O 2 release from sinusoids to hepato an increase in the leukocytes adhering to the sinusoidal tocytes. The observed decreases in the O 2 transport paramewall and a decrease in the number of sinusoids displaying ters were prominent in pericentral sinusoids. All of these blood flow. 5 These results imply a deterioration of O 2 transphenomena were further aggravated by the administration of port in hepatic microcirculation; however, there has as yet N w -nitro-L-arginine methyl ester (L-NAME) (5 mg/kg/h) plus been no experimental evidence of this. LPS, and by aminoguanidine (AMG) (5 mg/kg/h) plus LPS,Dual-spot microspectroscopy is useful for evaluating heand these could be reversed by the concomitant administrapatic microcirculation to quantify sinusoidal O 2 transport tion of L-arginine (L-Arg) (100 mg/kg/h). These results suggest parameters such as red blood cell velocity, intrasinusoidal that deterioration of hepatic oxygen transport and liver funchemoglobin (Hb) concentration, Hb oxygenation, and the tion induced by endotoxin can be ameliorated by NO. (HEPArate of O 2 transfer from sinusoids to hepatocytes. 18 In the TOLOGY 1997;26:336-342.) present study, we used this method to quantitatively study periportal and pericentral sinusoidal O 2 transport in endoCholestatic liver injury is commonly observed in septic toxin-infused rat livers. patients. 1 Endotoxin, a major exogenous product of bacteria, causes similar morphological and functional alterations in MATERIALS AND METHODS the liver. 2 Because the addit...

Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide‐induced fulminant hepatic failure

“…In the current study, the dose of l ‐NAME (20 mg kg −1 day −1 ) was sufficient to cause very substantial inhibition of NOS in rats with fulminant hepatic failure and the outcome may be related to the degree of NO inhibition. However, previous reports demonstrated that even much lower doses of l ‐NAME (0·5–5 mg kg −1 ) can induce hepatic microcirculatory dysfunction during endotoxaemia [46,47] and the degree of NOS inhibition did not alter the outcome following infection [48]. Whether lower doses of NOS inhibition by L‐NAME may produce different effects awaits further investigation.…”

Safety Assessment of Liver-Targeted Hydrodynamic Gene Delivery in Dogs

“…The index of blood volume in regional hepatic tissue [IHB] and the index of blood oxygenation in regional hepatic tissue [ISO 2 ] were monitored using a reflectance spectrophotometry system (TS-200, Sumitomo Electric, Osaka, Japan) before, during, and after hydrodynamic injection at a constant flow rate of 1.2 ml/sec as previously reported [17].…”

Nitric Oxide and Redox Regulation in the Liver: Part II. Redox Biology in Pathologic Hepatocytes and Implications for Intervention

“…Specifically, nonspecific NOS inhibition (L-NMMA and L-NAME) results in increased hepatic damage, while NO donors ameliorate this damage [8, 47, 48, 65, 73]. Although the results are not exactly clear, inhibition of iNOS has been noted to increase hepatic apoptosis [128] and limit PMN accumulation [52].…”