Angiotensin-Converting Enzyme Inhibitor Enhances Liver Regeneration Following Partial Hepatectomy : Involvement of Bradykinin B_2 and Angiotensin AT_1 Receptors(Pharmacology)
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概要
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Angiotensin-converting enzyme (ACE) inhibitor enhances the liver regeneration in rats after partial hepatectomy (PH), though the precise mechanisms are unknown. To determine the roles of bradykinin and angiotensin II in the ACE inhibitor-induced enhancement of liver regeneration, we investingated effects of lisinopril (ACE inhibitor), candesartan and losartan (angiotensin II type 1 (AT_1) receptor antagonists) and icatibant (bradykinin B_2 receptor antagonist) on the hepatic regenerative response to 70% PH in the rat. The liver regeneration was evaluated by measuring the frequency of 5-bromo-2'-deoxyuridine (BrdU) incorporation into hepatocyte nuclei 48 h after PH. We found that administration of candesartan or losartan, as well as lisinopril, enhanced BrdU incorporation after PH, and the lisinopril-induced enhancement was inhibited in part (40%) by icatibant. PH induced the expression of hepatocyte growth factor (HGF) mRNA in remnant liver, and this PH-induced up-regulation of HGF mRNA was further enhanced not only by lisinopril but also by candesartan and losartan. Administration of icatibant inhibited up to 40% of the lisinopril-induced up-regulation of HGF mRNA. These results suggest that the blockade of the renin-angiotensin system by either ACE inhibitor or AT_1 receptor antagonist enhances the hepatic regenerative response to PH, probably through an augmentation of hepatic HGF production. In addition to this mechanism, the activation of B_2 receptors may also be involved in the ACE inhibitor-induced enhancement of hepatic regenerative response.
- 公益社団法人日本薬学会の論文
- 2007-03-01
著者
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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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YAYAMA Katsutoshi
Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin Uni
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MIYAGI Ryoko
Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin Uni
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SUGIYAMA Kaori
Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin Uni
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OKAMOTO Hiroshi
Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin Uni
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Okamaoto H
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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Okamoto H
Department Of Systems And Control Engineering Anan National College Of Technology
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Sugiyama Kaori
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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岡本 宏巳
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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屋山 勝俊
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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Miyagi Ryoko
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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Okamoto Hiroshi
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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