Carbon monoxide overproduced by heme oxygenase-1 causes a reduction of vascular resistance in perfused rat liver

Yoshiyuki Wakabayashi, Rina Takamiya, Akira Mizuki, Takanori Kyokane, Nobuhito Goda, Tokio Yamaguchi, Shinji Takeoka, Eishun Tsuchida, Makoto Suematsu, Yuzuru Ishimura

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62 Citations (Scopus)

Abstract

This study aimed to examine whether livers overexpressing heme oxygenase (HO)-1 could alter the vascular resistance through the vasorelaxing action of carbon monoxide (CO). The relationship among HO-1 expression, CO generation, and the vascular resistance was assessed in perfused rat livers pretreated with hemin, an inducer of HO-1. At 18 h after the hemin treatment, livers displayed marked increases in HO-1 expression in hepatocytes and venous CO flux and a reduction of the basal resistance. The reduction of the resistance in hemin-treated livers was canceled by administration of oxyhemoglobin, a reagent trapping both CO and nitric oxide (NO), but not by methemoglobin, which captures NO but not CO. Liposome-encapsulated oxyhemoglobin, which cannot access the space of Disse, did not cause vasoconstriction. Furthermore, these livers became less sensitive to endothelin-1, a vasoconstrictive peptide, than the untreated controls through mechanisms involving CO. On the other hand, at 12 or 24 h after the treatment when the HO-1 induction was not accompanied by CO overproduction, neither a decrease in the basal resistance nor vascular hyporeactivity to endothelin-1 was observed. These results suggest that CO overproduced in the extrasinusoidal compartment is a determinant of the HO-1-mediated vasorelaxation in the liver.

Original languageEnglish
Pages (from-to)G1088-G1096
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume277
Issue number5 40-5
Publication statusPublished - 1999 Nov 1

Keywords

  • Cytochrome P-450
  • Heat shock protein 32
  • Hemoglobin
  • Hepatic sinusoids
  • Methemoglobin

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Wakabayashi, Y., Takamiya, R., Mizuki, A., Kyokane, T., Goda, N., Yamaguchi, T., Takeoka, S., Tsuchida, E., Suematsu, M., & Ishimura, Y. (1999). Carbon monoxide overproduced by heme oxygenase-1 causes a reduction of vascular resistance in perfused rat liver. American Journal of Physiology - Gastrointestinal and Liver Physiology, 277(5 40-5), G1088-G1096.