CO overproduction is responcible for heme oxygenase 1-mediated microvascular hyporeactivity in perfused rat liver

Y. Wakabayashi, R. Takamiya, A. Mizuki, M. Suematsu, Y. Ishimura

Research output: Contribution to journalArticle

Abstract

Heme oxygenase (HO)-1 is a stress-inducible protein which oxidatively degrades heme into biliverdin and CO. This study aimed to examine whether the HO-1 induction changes hepatic vascular responses through vasorelaxing action of CO. Isolated perfused rat livers were used to assess the vascular resistance under the unstimulated baseline and ET-1-stimulated conditions. After exposed to 40 μmol/kg of hemin, the liver increased HO-1 expression time-dependently that peaked at 12 hrs. Under these circumstances, neither a reduction of the vascular resistance nor elevation of the venous CO flux was detectable. At 18 hrs, the liver displayed a decrease in the baseline vascular resistance as well as in the ET-induced vasoconstrictive response in concert with a 4-fold increase in the CO flux. According to immunohistochemical analysis, both hepatocytes and Kupffer cells constituted major cellular components responsible for the HO-1 overexpression. The vascular hyporeactivity at 18 hrs was abolished by administration of zinc protoporphyrin IX, an HO inhibitor. Furthermore, the ZnPP-induced disappearance of the vascular hyporeactivity was restored in part by supplement of CO at micromolar levels. Laser confocal microangiography showed that a decreasing sensitivity to ET in sinusoidal vessels is responsible for this event. These results provide evidence that overproduction of CO accounts for the mechanisms for HO-1-mediated microvascular hyporeactivity, suggesting its pathophysiological significance for functional alterations in hepatoportal vascular system under stress conditions.

Original languageEnglish
JournalFASEB Journal
Volume12
Issue number5
Publication statusPublished - 1998 Mar 20

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Wakabayashi, Y., Takamiya, R., Mizuki, A., Suematsu, M., & Ishimura, Y. (1998). CO overproduction is responcible for heme oxygenase 1-mediated microvascular hyporeactivity in perfused rat liver. FASEB Journal, 12(5).