Role of nitric oxide in endotoxin-induced hepatic microvascular dysfunction in rats chronically fed ethanol

Yoshinori Horie, Hiroyuki Kimura, Shinzo Kato, Eiji Ohki, Hironao Tamai, Yoshiyuki Yamagishi, Hiromasa Ishii

Research output: Contribution to journalArticle

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Abstract

Background: Nitric oxide (NO) appears to be involved in the pathogenesis of endotoxin-induced liver injury. However, little is known about how NO acts on the hepatic microcirculation, especially in alcohol-fed animals. We examined the roles of NO in endotoxin-induced hepatic microvascular dysfunction in control and ethanol-fed rats. Methods: One lobe of the liver was observed with an intravital microscope. Flow velocity of fluorescein isothiocyanate-labeled erythrocytes in sinusoids was measured with an off- line velocimeter. Portal pressure and mean arterial pressure also were measured. Results: After administration of endotoxin to control, the flow velocity decreased after 30 min. Portal pressure increased after 45 min. However, in ethanol-fed rats, both the flow velocity and portal pressure temporarily increased in the early phase. Thereafter, the flow velocity decreased and portal pressure increased. At 30 min after administration of the endotoxin, pretreatment with 10 mg/kg of an NO synthase inhibitor, N(G)- monomethyl-L-arginine (L-NMMA), enhanced the endotoxin-induced decrease in the velocity of erythrocytes in the midzonal region of both control and ethanol-fed rats. Although 0.5 mg/kg of L-NMMA enhanced the endotoxin-induced reduction of erythrocyte velocity in the midzonal region of ethanol-fed rats, L-NMMA enhanced the endotoxin-induced reduction of erythrocyte velocity in the pericentral region of control rats. At 60 min after the endotoxin administration, L-NMMA did not affect the endotoxin-induced decrease of erythrocyte velocity in either control or ethanol-fed rats. Although 10 mg/kg of L-NMMA increased mean arterial pressure both in control and ethanol-fed rats, 0.5 mg/kg of L-NMMA did not change mean arterial pressure in either control or ethanol-fed rats. Conclusions: These results suggest that NO is involved in endotoxin-induced hepatic microvascular dysfunction, which may contribute to the sequential liver injury, especially in alcohol-fed animals.

Original languageEnglish
Pages (from-to)845-851
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume24
Issue number6
Publication statusPublished - 2000 Jun

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Endotoxins
Rats
Nitric Oxide
Ethanol
omega-N-Methylarginine
Liver
Portal Pressure
Flow velocity
Erythrocytes
Arterial Pressure
Animals
Alcohols
Rat control
Microcirculation
Velocimeters
Wounds and Injuries
Fluorescein
Nitric Oxide Synthase
Arginine
Microscopes

Keywords

  • Erythrocyte velocity
  • Fluorescein isothiocyanate
  • Intravital microscope
  • Portal pressure

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Role of nitric oxide in endotoxin-induced hepatic microvascular dysfunction in rats chronically fed ethanol. / Horie, Yoshinori; Kimura, Hiroyuki; Kato, Shinzo; Ohki, Eiji; Tamai, Hironao; Yamagishi, Yoshiyuki; Ishii, Hiromasa.

In: Alcoholism: Clinical and Experimental Research, Vol. 24, No. 6, 06.2000, p. 845-851.

Research output: Contribution to journalArticle

Horie, Yoshinori ; Kimura, Hiroyuki ; Kato, Shinzo ; Ohki, Eiji ; Tamai, Hironao ; Yamagishi, Yoshiyuki ; Ishii, Hiromasa. / Role of nitric oxide in endotoxin-induced hepatic microvascular dysfunction in rats chronically fed ethanol. In: Alcoholism: Clinical and Experimental Research. 2000 ; Vol. 24, No. 6. pp. 845-851.
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AU - Horie, Yoshinori

AU - Kimura, Hiroyuki

AU - Kato, Shinzo

AU - Ohki, Eiji

AU - Tamai, Hironao

AU - Yamagishi, Yoshiyuki

AU - Ishii, Hiromasa

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AB - Background: Nitric oxide (NO) appears to be involved in the pathogenesis of endotoxin-induced liver injury. However, little is known about how NO acts on the hepatic microcirculation, especially in alcohol-fed animals. We examined the roles of NO in endotoxin-induced hepatic microvascular dysfunction in control and ethanol-fed rats. Methods: One lobe of the liver was observed with an intravital microscope. Flow velocity of fluorescein isothiocyanate-labeled erythrocytes in sinusoids was measured with an off- line velocimeter. Portal pressure and mean arterial pressure also were measured. Results: After administration of endotoxin to control, the flow velocity decreased after 30 min. Portal pressure increased after 45 min. However, in ethanol-fed rats, both the flow velocity and portal pressure temporarily increased in the early phase. Thereafter, the flow velocity decreased and portal pressure increased. At 30 min after administration of the endotoxin, pretreatment with 10 mg/kg of an NO synthase inhibitor, N(G)- monomethyl-L-arginine (L-NMMA), enhanced the endotoxin-induced decrease in the velocity of erythrocytes in the midzonal region of both control and ethanol-fed rats. Although 0.5 mg/kg of L-NMMA enhanced the endotoxin-induced reduction of erythrocyte velocity in the midzonal region of ethanol-fed rats, L-NMMA enhanced the endotoxin-induced reduction of erythrocyte velocity in the pericentral region of control rats. At 60 min after the endotoxin administration, L-NMMA did not affect the endotoxin-induced decrease of erythrocyte velocity in either control or ethanol-fed rats. Although 10 mg/kg of L-NMMA increased mean arterial pressure both in control and ethanol-fed rats, 0.5 mg/kg of L-NMMA did not change mean arterial pressure in either control or ethanol-fed rats. Conclusions: These results suggest that NO is involved in endotoxin-induced hepatic microvascular dysfunction, which may contribute to the sequential liver injury, especially in alcohol-fed animals.

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KW - Fluorescein isothiocyanate

KW - Intravital microscope

KW - Portal pressure

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