| Project/Area Number |
10670509
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokai University |
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Principal Investigator |
WATANABE Norihito Tokai University School of Medicine, Associate Professor, 医学部, 助教授 (90167156)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIZAKI Yasuhiro Tokai University School of Medicine, Assistant Professor, 医学部, 講師 (80237693)
KAGAWA Tatehiro Tokai University School of Medicine, Assistant Professor, 医学部, 講師 (30245469)
MATSUZAKI Shohei Tokai University School of Medicine, Professor, 医学部, 教授 (40110902)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | hepatic hemodynamics / hepatic microcirculation / portal hypertension / sinusoidal endothelial cell / SEF / endothelin-1 / endothelin receptors / ethanol / 肝循環 / 肝硬変 / エンドセリン / BQ-123 / video-enhanced microscopy |
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| Research Abstract |
Endothelin (ET)-1, a potent vasoconstrictor is increased in liver cirrhosis, indicating that ET-1 may be involved in the pathophysiology of portal hypertension. Here we examined effects of ET (ET_A and ET_B) receptors antagonists on hepatic hemodynamics and SEF in normal and portal hypertensive rats. Methods : BQ-123, an ET_A receptor antagonist, or BQ-788, an ET_B receptor antagonist was infused to normal and cirrhotic rats at the rate of 10 nmol/min for 10 min. Ethanol was infused at the rate of 8 mg/min for 60 min. Portal pressure and hepatic tissue blood flow were measured using a hydromanometer and a laser Doppler blood flowmeter, respectively. Plasma ET-1 levels were determined by RIA.The sinusoids fixed by the perfusion technique were observed SEM.The expression of ET_A and ET_B receptors was examined by the indirect immunoperoxidase method. Results : Acute ethanol infusion caused a significant increase in portal pressure and decrease in hepatic tissue blood flow, and SEF were m
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arkedly decreased in number and in diameter. These ethanol-induced changes were inhibited by BQ-123. In cirrhotic rats, the portal pressure was markedly increased to be 16.6±1.5 cm H_2O, and plasma ET-1 levels became higher than those in normal. When BQ-123 was infused, the portal pressure showed a marked reduction by more than 2 cm H_2Oin both normal and cirrhotic rats. On the other hand, the decrease in portal pressure was not found in the BQ-788 infused groups. BQ-123 induced marked dilatation of SEF in zone 1 and zone 3. The diameter of SEF was almost three times longer than that of normal SEF.SEF were extremely decreased and almost disappeared in cirrhosis. However, SEF could be observed in some sinusoids by treatment with BQ-123. Immunohistochemically, ET-1 was evenly distributed alpng the sinusoidal walls in normal rats, and remarkably enhanced in cirrhosis. The expression of ET_A and ET_B were found to be augmented in cirrhosis. Conclusions : The action of ET-1 via ET_A receptors rather than ET_B receptors may be associated with the regulation of portal pressure as well as the motion of SEF in the hepatic microcirculation and in the mechanisms of portal hypertension. Less
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