Changes in circulatory status and transport function of the liver induced by reactive oxygen species.
To elucidate the pathogenesis of microcirculatory disturbance of the liver after ischemia and reperfusion, the effect of reactive oxygen species on hepatic circulatory status and transport function for a cholephilic compound was studied in an isolated perfused rat liver. Perfusion of the liver with a medium containing hypoxanthine and xanthine oxidase significantly increased the portal pressure, with concomitant decrease in intrahepatic vascular volume and hepatic uptake of bromosulfophthalein (BSP). Similar changes were also elicited by infusion of serotonin, which induces contraction of sinusoidal endothelial cells. Either superoxide dismutase or catalase added in the perfusion medium partially inhibited the oxidase-induced changes in portal pressure, vascular volume of hepatic sinusoid, and BSP transport. In the presence of superoxide dismutase, either catalase or erythrocytes inhibited the oxidase-induced changes completely. These results indicated that superoxide anion and hydrogen peroxide might induce contraction of hepatic resistance vessels, capacitance vessels, and/or sinusoidal endothelial cells and that this contraction decreased the vascular bed in the liver and the time for interaction of circulation substrates with hepatocytes, thereby decreasing hepatic transport for cholephilic ligands such as BSP.
Department of Surgery, Kumamoto University School of Medicine, Japan.
S
S
Kawamoto
S
S
Tashiro
Y
Y
Miyauchi
M
M
Inoue
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001790:Blood Physiological Phenomena; D002374:Catalase / Q000494:pharmacology; D003250:Constriction; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D012709:Serum Albumin / Q000494:pharmacology; D013448:Sulfobromophthalein / Q000493:pharmacokinetics; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D017382:Reactive Oxygen Species; D012709:Serum Albumin; D013448:Sulfobromophthalein; D012701:Serotonin; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase