Endotoxin-Induced Enhancement of Angiotensinogen Synthesis in hte Liver : Decreased Response Following Repeated Endotoxin Exposure
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概要
- 論文の詳細を見る
To understand the mechanisms responsible for lipopolysaccharide (LPS)-induced enhancement of angiotensinogen synthesis in the liver, studies were carried out in rats with repeated doses of LPS. The administration of sublethal dose (50 μg, i.p.) of LPS to rats resulted in increase in serum levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6), which attained their maximal levels by 1 and 2-4 h, respectively. Serum levels of angiotensinogen and α_2-macroglobulin, a typical acute-phase protein in the rat, were also increased by a primary LPS challenge, and their maximal levels for the formation of TNF and IL-6 were delayed with peaks at 12 and 48 h, respectively. Repeated i.p. administration of LPS (50 μg/d) for 5 consecutive days induced a hyporesponsiveness to its subsequent administration in terms of increasing serum TNF, IL-6 and α_2-macroglobulin. In these LPS-tolerant rats, either LPS-induced elevation of angiotensinogen concentration in serum or angiotensinogen mRNA levels in liver was completely eliminated. Angiotensinogen synthesis in rat hepatoma H4 cells was enhanced in vitro by the addition of sera which had been collected 2 or 4 h after a primary injection of LPS, while not by sera collected from LPS-pretreated rats after a secondary LPS exposure. These results indicate that LPS-induced enhancement of angiotensinogen synthesis in the liver is desensitized in rats after repetitive LPS exposure, presumably by the failure of LPS-induced IL-6 production.
- 社団法人日本薬学会の論文
- 1993-09-15
著者
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岡本 博
神戸学院大学薬学部 生命薬学部門 循環器薬理学研究室
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横山 和幸
Department Of Pharmacology Faculty Of Pharmaceutical Sciences
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屋山 勝俊
神戸学院大学薬学部 生命薬学部門 循環器薬理学研究室
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屋山 勝俊
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University
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鷹野 正興
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University
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岡本 博
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University
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伊藤 徳夫
Department of Pharmacology, Faculty of Pharmaceutical Sciences
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伊藤 徳夫
Department Of Pharmacology Faculty Of Pharmaceutical Sciences
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Takano M
Tohoku Pharmaceutical University
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鷹野 正興
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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松井 貴史
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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Okamoto H
Faculty Of Pharmacy Meijo University
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Takano M
Department Of Pharmacology Faculty Of Pharmaceutical Sciences And High Technology Research Center
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屋山 勝俊
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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Yayama Katsutoshi
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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