| Project/Area Number |
06454264
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University School of Medicine |
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Principal Investigator |
SUEMATSU Makoto Dept Biochem.Keio Univ.Ass Professor., 医学部, 専任講師 (00206385)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Norihito Dept.Med.Tokai Univ.Ass Professor., 医学部, 助教授 (90167156)
ISHIMURA Yuzuru Dept Biochem.Keio Univ.Professor., 医学部, 教授 (40025599)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1994: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | carbon monoxide / nitric oxide / heme oxygenase / microcirculation / Ito cell / liver / cholestasis / bilirubin / heme oxygenase / 一酸化窒素ラジカル / cGMP / 肝類洞循環 |
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| Research Abstract |
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 monitor sinusoidal lining and fat-storing Ito cells, alternately. In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min /g liver. Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 muM) 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 muM) or a cGMP analogue 8-bromo-cGMP (1 muM) 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.
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