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

Fingerprint

heme oxygenase (biliverdin-producing)
Heme Oxygenase-1
Carbon Monoxide
blood vessels
Liver
Rats
liver
Blood Vessels
rats
Vascular Resistance
heme
Biliverdine
Fluxes
Kupffer cells
Heme Oxygenase (Decyclizing)
Hemin
protoporphyrin
Kupffer Cells
oxygenases
Heat-Shock Proteins

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).

CO overproduction is responcible for heme oxygenase 1-mediated microvascular hyporeactivity in perfused rat liver. / Wakabayashi, Y.; Takamiya, R.; Mizuki, A.; Suematsu, M.; Ishimura, Y.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

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, vol. 12, no. 5.
Wakabayashi, Y. ; Takamiya, R. ; Mizuki, A. ; Suematsu, M. ; Ishimura, Y. / CO overproduction is responcible for heme oxygenase 1-mediated microvascular hyporeactivity in perfused rat liver. In: FASEB Journal. 1998 ; Vol. 12, No. 5.
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