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

Wakabayashi, Y., Takamiya, R., Mizuki, A., Kyokane, T., Goda, N., Yamaguchi, T., ... 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).

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.
@article{aed070e0cafd4944bab5dbba7a492f3d,
title = "Carbon monoxide overproduced by heme oxygenase-1 causes a reduction of vascular resistance in perfused rat liver",
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.",
keywords = "Cytochrome P-450, Heat shock protein 32, Hemoglobin, Hepatic sinusoids, Methemoglobin",
author = "Yoshiyuki Wakabayashi and Rina Takamiya and Akira Mizuki and Takanori Kyokane and Nobuhito Goda and Tokio Yamaguchi and Shinji Takeoka and Eishun Tsuchida and Makoto Suematsu and Yuzuru Ishimura",
year = "1999",
month = "11",
language = "English",
volume = "277",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5 40-5",

}

TY - JOUR

T1 - Carbon monoxide overproduced by heme oxygenase-1 causes a reduction of vascular resistance in perfused rat liver

AU - Wakabayashi, Yoshiyuki

AU - Takamiya, Rina

AU - Mizuki, Akira

AU - Kyokane, Takanori

AU - Goda, Nobuhito

AU - Yamaguchi, Tokio

AU - Takeoka, Shinji

AU - Tsuchida, Eishun

AU - Suematsu, Makoto

AU - Ishimura, Yuzuru

PY - 1999/11

Y1 - 1999/11

N2 - 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.

AB - 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.

KW - Cytochrome P-450

KW - Heat shock protein 32

KW - Hemoglobin

KW - Hepatic sinusoids

KW - Methemoglobin

UR - http://www.scopus.com/inward/record.url?scp=18244420268&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18244420268&partnerID=8YFLogxK

M3 - Article

C2 - 10564116

AN - SCOPUS:18244420268

VL - 277

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 5 40-5

ER -