Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide-mediated microvascular relaxation

Nobuhito Goda, Kensuke Suzuki, Makoto Naito, Shinji Takeoka, Eishun Tsuchida, Yuzuru Ishimura, Takuya Tamatani, Makoto Suematsu

Research output: Contribution to journalArticlepeer-review

249 Citations (Scopus)


Carbon monoxide (CO) derived from heme oxygenase has recently been shown to play a role in controlling hepatobiliary function, but intrahepatic distribution of the enzyme is unknown. We examined distribution of two kinds of the heme oxygenase isoforms (HO-1 and HO-2) in rat liver immunohistochemically using monoclonal antibodies. The results showed that distribution of the two isoforms had distinct topographic patterns: HO-1, an inducible isoform, was observed only in Kupffer cells, while HO-2, a constitutive form, distributed to parenchymal cells, but not to Kupffer cells. Both isoforms were undetectable in hepatic stellate cells and sinusoidal endothelial cells. Of the two isoforms, HO-2 in the parenchymal cell rather than HO-1 in the Kupffer cell, appears to play a major role in regulation of microvascular tone. In the perfused liver, administration of HbO2, a CO-trapping reagent that can diffuse across the fenestrated endothelium into the space of Disse, elicited a marked sinusoidal constriction, while administration of a liposome-encapsulated Hb that cannot enter the space had no effect on the microvascular tone. These results suggest that CO evolved by HO-2 in the parenchymal cells, and, released to the extrasinusoidal space, served as the physiological relaxant for hepatic sinusoids.

Original languageEnglish
Pages (from-to)604-612
Number of pages9
JournalJournal of Clinical Investigation
Issue number3
Publication statusPublished - 1998 Feb 1
Externally publishedYes


  • Heme oxygenase-1
  • Heme oxygenase-2
  • Hemoglobin
  • Hepatic stellate cells
  • Kupffer cells

ASJC Scopus subject areas

  • General Medicine


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