Protective role of NO in hepatic microcirculatory dysfunction during endotoxemia

Abstract

Nitric oxide (NO) has been reported to have a protective function in attenuating hepatic injury during endotoxemia or sepsis. As a result, the role of NO in attenuating the hepatic microcirculatory alterations associated with endotoxemia was investigated in mice by in vivo microscopy. The livers were examined 2 h after intravenous injection of Escherichia coli 0111:B4 lipopolysaccharide (LPS) alone or in combination with inhibitors of the synthesis of NO, NG-nitro-L-arginine methyl ester or NG-monomethyl-L-arginine. In the animals treated with the combination of NO synthase inhibitors and LPS, leukocyte adherence was increased threefold above that in animals treated with LPS alone. This was accompanied by a 33% reduction in sinusoidal blood flow. Simultaneous administration of L-arginine, but not D-arginine, eliminated these microcirculatory disturbances. The results demonstrate that inhibition of LPS-stimulated NO production results in an early hepatic microvascular inflammatory response to a dose of endotoxin which by itself is scarcely inflammatory. This suggests that NO plays a significant role in stabilizing the hepatic microcirculation during endotoxemia, thereby helping to protect the liver from ischemia and leukocyte-induced oxidative injury.

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

“…The inhibition of NO synthesis in endotoxemia promoted the above phenomena. 5 The re-The changes in hepatic microcirculation appeared to be well correlated with hepatic injuries indicated by biochemical and sults of the present study suggest that the inhibition of NO production by L-NAME causes deterioration of hepatic func-histological findings. Thus, NO induced by LPS improved the hepatic microcirculation under endotoxemia.…”

“…Although the dual-spot microspectroscopy more sharply demonstrated changes in the hepatic testinal injuries. 29 McCuskey 6 and Nishida et al 5 reported that a bolus administration of LPS causes the following: 1) microcirculation than reflectance spectrophotometry, findings (ISO 2 and IHb) of the reflectance spectrophotometry increases in the number of leukocytes and platelets adhering to the sinusoidal wall; and 2) decreases in the number of were grossly similar to those of the SO 2 and Hb content in sinusoids measured by the microspectroscopy, respectively. sinusoids with blood flow.…”

“…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.…”

Stimulation of inducible nitric oxide synthase in rat liver by hyaluronan fragments

“…The role of NO in acute liver injury and in conditions in which inflammation is prominent has been examined extensively. [46][47][48][49] In some models, NO and/or its metabolic byproducts accelerate injury, while, in other instances, NO appears to be protective. 19,49 In chronic liver injury, while iNOS and NO have been identified, their pathogenic roles have been less well elucidated.…”

“…[46][47][48][49] In some models, NO and/or its metabolic byproducts accelerate injury, while, in other instances, NO appears to be protective. 19,49 In chronic liver injury, while iNOS and NO have been identified, their pathogenic roles have been less well elucidated. 50 The potential relevance of HA fragment induction of iNOS in liver is manifold; however, its importance to the pathogenesis of liver diseases requires further investigation.…”