ROLE OF NITRIC-OXIDE IN OXYGEN-TRANSPORT IN RAT-LIVER SINUSOIDS DURING ENDOTOXEMIA

To evaluate the role of nitric oxide (NO) in hepatic microcirculation and liver injury during endotoxemia, we studied O-2 transport in the h epatic microcirculation of endotoxin-fused rats. Rats were continuousl y infused with Escherichia coli lipopolysaccharide (LPS) (0.8 mg/kg/h) for 7 hours. LPS increased the plasma levels of NO2- + NO3- and aspar tate transaminase (AST), and decreased the bile Row rate and hepatic a denosine triphosphate (ATP) level. Hepatic microcirculation was evalua ted by two methods: reflectance spectrophotometry showed a decrease in the oxygenation of hemoglobin (Hb) in the liver, and dual-spot micros pectroscopy indicated that LPS administration decreased blood velocity , the oxygenation of Hb, and Oz release from sinusoids to hepatocytes. The observed decreases in the Oz transport parameters were prominent in pericentral, sinusoids. AU of these phenomena were further aggravat ed by the administration of N-w-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg/h) plus LPS, and by aminoguanidine (AMG) (5 mg/kg/h) plus LP S, and these could be reversed by tile concomitant administration of L -arginine (L-Arg) (100 mg/kg/h). These results suggest that deteriorat ion of hepatic oxygen transport and liver function induced by endotoxi n can be ameliorated by NO.