Enhancement of Endothelial Nitric Oxide Production by Chenodeoxycholic Acids in Patients with Hepatobiliary Diseases
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概要
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The purpose of this study was to clarify whether physiological concentrations of bile acids could affect endothelial nitric oxide production. We investigated the relationships between clinical concentrations of individual bile acids observed in patients with hepatobiliary diseases and endothelial nitric oxide production induced by each bile acid. Fifteen serum bile acids were measured using high-performance liquid chromato-graphy combined with enzymatic fluorometry in 8 patients with liver cirrhosis, obstructive jaundice, and 8 healthy subjects. The effects of individual bile acids on nitric oxide production were examined in human umbilical endothelial cells by measuring the concentration of NO2− in the cultured medium. NO release in the blood was also determined by measuring the NO2− / NO3− concentration in these patients. In patients with hepatobiliary diseases, the plasma concentrations of chenodeoxycholic acid, ursodeoxycholic acid and cholic acid (free acid, taurine and glycine conjugates) were markedly elevated. Incubation of cells with chenodeoxycholic acid and deoxycholic acid (free acid, taurine and glycine conjugates) enhanced NO2− production in a concentration-dependent manner, while cholic acid (free and its conjugates) did not. The effects of individual bile acids on nitric oxide production were additive. Patients with liver cirrhosis and obstructive jaundice had higher plasma levels of NO2 − / NO3− levels than the control subjects. These results suggest that increased plasma concentrations of chenodeoxycholic acid (free, taurine and glycine conjugates) in patients with hepatobiliary diseases may induce endothelial nitric oxide production. Thus, nitric oxide production induced by bile acids may be involved in the pathogenesis of circulatory abnormalities in patients with liver diseases.
著者
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Iwasawa Kuniaki
Department Of Cardiovascular Medicine The University Of Tokyo
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Komatsu Yutaka
Department Of Gastroenterology The University Of Tokyo
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Omata Masao
Department Of Cardiology Narita Red Cross Hospital
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Hirata Yasunobu
Department Of Advanced Clinical Science And Therapeutics Cardiovascular Medicine Graduate School Of
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Okuda Yukichi
Department Of Internal Medicine Institute Of Clinical Medicine University Of Tsukuba
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Matsumoto Akihiro
Department Of Cardiothoracic Surgery The University Of Tokyo
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Hirose Ken
Department Of Mathematics School Of Science And Engineering Waseda University
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Miyamoto Kenichi
Department Of Chemistry For Materials Faculty Of Engineering And Graduate School Of Engineering Mie
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Nagai Ryozo
Department Cardiovascular Medicine The University Of Tokyo Hospital
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Nakajima Toshiaki
Department Of Cardiology Tokyo University
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SHIRATORI Yasushi
Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine and Dentistry, Okayama
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Iida Haruko
Department of Cardiovascular Medicine, School of Medicine, University of Tokyo
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Iwasawa Kuniaki
Department of Cardiovascular Medicine, School of Medicine, University of Tokyo
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Goto Atsuo
Department of Gastroenterology, School of Medicine, University of Tokyo
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Chisaki Keigo
Department of Cardiovascular Medicine, School of Medicine, University of Tokyo
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Tada Minoru
Department of Gastroenterology, School of Medicine, University of Tokyo
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Tada Minoru
Department of Applied Chemistry, Faculty of Engineering, Doshisha University
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Matsumoto Akihiro
Department of Cardiovascular Medicine, School of Medicine, University of Tokyo
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Omata Masao
Department of Gastroenterology, School of Medicine, University of Tokyo
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Miyamoto Kenichi
Department of Clinical Pharmaceutics, Graduate School of Natural Sciences and Technology, Kanazawa University
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