Carbon monoxide: An endogenous modulator of sinusoidal tone in the perfused rat liver

Makoto Suematsu*, Nobuhito Goda, Tsuyoshi Sano, Satoshi Kashiwagi, Tsuyoshi Egawa, Yuichi Shinoda, Yuzuru Ishimura

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

361 Citations (Scopus)


Heme oxygenase is a heme-oxidizing enzyme which generates biliverdin and carbon monoxide (CO). The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation. Microvasculature of the isolated perfused rat liver was visualized by dual-color digital microfluorography to alternately monitor sinusoidal lining and fat-storing Ito cells. In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min per gram of liver. Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 μM) eliminated the baseline CO generation, and the vascular resistance exhibited a 30% elevation concurrent with discrete patterns of constriction in sinusoids and reduction of the sinusoidal perfusion velocity. The major sites of the constriction corresponded to local sinusoidal segments colocalized with Ito cells which were identified by imaging their vitamin A autofluorescence. The increase in the vascular resistance and sinusoidal constriction were attenuated significantly by adding CO (1 μM) or a cGMP analogue 8-bromo-cGMP (1 μM) in the perfusate. From these findings, we propose that CO can function as an endogenous modulator of hepatic sinusoidal perfusion through a relaxing mechanism involving Ito cells.

Original languageEnglish
Pages (from-to)2431-2437
Number of pages7
JournalJournal of Clinical Investigation
Issue number5
Publication statusPublished - 1995 Nov
Externally publishedYes


  • Ito cells
  • cGMP
  • heme oxygenase
  • microcirculation
  • nitric oxide

ASJC Scopus subject areas

  • General Medicine


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