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.
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Tokyo 160, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Wakabayashi
authors.forename: R
authors.initials: R
authors.lastname: Takamiya
authors.forename: A
authors.initials: A
authors.lastname: Mizuki
authors.forename: T
authors.initials: T
authors.lastname: Kyokane
authors.forename: N
authors.initials: N
authors.lastname: Goda
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Takeoka
authors.forename: E
authors.initials: E
authors.lastname: Tsuchida
authors.forename: M
authors.initials: M
authors.lastname: Suematsu
authors.forename: Y
authors.initials: Y
authors.lastname: Ishimura
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D066298:In Vitro Techniques; D008081:Liposomes; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008706:Methemoglobin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010108:Oxyhemoglobins / Q000494:pharmacology; D010477:Perfusion; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D008081:Liposomes; D010108:Oxyhemoglobins; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D009569:Nitric Oxide; D006427:Hemin; D002248:Carbon Monoxide; D008706:Methemoglobin; D003577:Cytochrome P-450 Enzyme System; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D019331:NG-Nitroarginine Methyl Ester