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

    Research output: Contribution to journalArticle

    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
    JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
    Volume277
    Issue number5 40-5
    Publication statusPublished - 1999 Nov

    Fingerprint

    Heme Oxygenase-1
    Carbon Monoxide
    Vascular Resistance
    Liver
    Hemin
    Oxyhemoglobins
    Endothelin-1
    Nitric Oxide
    Carbon Cycle
    Methemoglobin
    Vasoconstriction
    Vasodilation
    Liposomes
    Hepatocytes
    Peptides
    Therapeutics

    Keywords

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

    ASJC Scopus subject areas

    • Gastroenterology
    • Physiology
    • Physiology (medical)

    Cite this

    Carbon monoxide overproduced by heme oxygenase-1 causes a reduction of vascular resistance in perfused rat liver. / Wakabayashi, Yoshiyuki; Takamiya, Rina; Mizuki, Akira; Kyokane, Takanori; Goda, Nobuhito; Yamaguchi, Tokio; Takeoka, Shinji; Tsuchida, Eishun; Suematsu, Makoto; Ishimura, Yuzuru.

    In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 277, No. 5 40-5, 11.1999.

    Research output: Contribution to journalArticle

    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, vol. 277, no. 5 40-5.
    Wakabayashi, Yoshiyuki ; Takamiya, Rina ; Mizuki, Akira ; Kyokane, Takanori ; Goda, Nobuhito ; Yamaguchi, Tokio ; Takeoka, Shinji ; Tsuchida, Eishun ; Suematsu, Makoto ; Ishimura, Yuzuru. / Carbon monoxide overproduced by heme oxygenase-1 causes a reduction of vascular resistance in perfused rat liver. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 1999 ; Vol. 277, No. 5 40-5.
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