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 O2 transport in the hepatic microcirculation of endotoxin-infused rats. Rats were continuously infused with Escherichia coli lipopolysaccharide (LPS) (0.8 mg/kg/h) for 7 hours. LPS increased the plasma levels of NO2- + NO3- and aspartate transaminase (AST), and decreased the bile flow rate and hepatic adenosine triphosphate (ATP) level. Hepatic microcirculation was evaluated by two methods: reflectance spectrophotometry showed a decrease in the oxygenation of hemoglobin (Hb) in the liver, and dual-spot microspectroscopy indicated that LPS administration decreased blood velocity, the oxygenation of Hb, and O2 release from sinusoids to hepatocytes. The observed decreases in the O2 transport parameters were prominent in pericentral sinusoids. All of these phenomena were further aggravated 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 LPS, and these could be reversed by the concomitant administration of L-arginine (L-Arg) (100 mg/kg/h). These results suggest that deterioration of hepatic oxygen transport and liver function induced by endotoxin can be ameliorated by NO.
Huang
T P
TP
First Department of Surgery, Osaka University Medical School, Japan.
Nishida
T
T
Kamike
W
W
Kosaka
H
H
Seiyama
A
A
Morimoto
Y
Y
Tanaka
S
S
Obunai
S
S
Takei
Y
Y
Shiga
T
T
Matsuda
H
H
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D019446:Endotoxemia / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006146:Guanidines; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D010100:Oxygen; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester