Drug Discovery for Overcoming Chronic Kidney Disease (CKD) : Development of Drugs on Endothelial Cell Protection for Overcoming CKD
スポンサーリンク
概要
- 論文の詳細を見る
Chronic kidney disease (CKD) is becoming a major public health problem worldwide. It is important to protect endothelial function in CKD treatment because injury of the endothelium is a critical event for the generation and progression of CKD. Recently, clinical studies showed that nifedipine, an antihypertensive drug, acts as a protective agent of endothelial cells (ECs). Nifedipine is reported to partially decompose to a nitrosonifedipine that has high reactivity against lipid-derived radicals in vitro. However, it is still unclear whether nitrosonifedipine is a biologically active agent against endothelial injury. We observed that nitrosonifedipine was converted to radical form by reaction with cultured ECs. The cumene hydroperoxide mediated cytotoxity was reduced by nitrosonifedipine in cultured human glomerular ECs (HGECs). Also nitrosonifedipine suppressed the expression of TNF-α–induced intercellular cell adhesion molecule-1 in HGECs. Chronic administration of Nω-nitro-<sc>L</sc>-arginine methyl ester (<sc>L</sc>-NAME) caused systemic arterial hypertension, endotherial injury, and renal dysfunction. In <sc>L</sc>-NAME–induced hypertensive rats, nitrosonifedipine treatment improved not only the acetylcholine-induced vasodilation of the aortic rings, but also renal dysfunction such as increasing the levels of serum creatinine and urinary protein excretion. Our preliminary data suggest that nitrosonifedipine is a new and useful drug for the treatment of CKD involving ameliorating effects on EC disorder.
- 社団法人 日本薬理学会の論文
- 2009-01-20
著者
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Tomita Shuhei
Department Of Pharmacology The Institute Of Health Bioscience The University Of Tokushima Graduate S
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Tomita Shuhei
徳島大学 ヘルスバイオサイエンス研究部薬理学
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Tomita Shuhei
徳島大学 ヘルスバイオサイエンス研究部薬理学分野
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Tomita Shuhei
Division Of Experimental Immunology Institute For Genome Research The University Of Tokushima Gradua
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Fukuhara Yayoi
Department of Pharmacology, IHBS, the University of TOKUSHIMA Graduate school
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Tamaki Toshiaki
Department of Pharmacology, IHBS, the University of TOKUSHIMA Graduate school
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ISHIZAWA Keisuke
Department of Pharmacology, The University of Tokushima Graduate School of Medical Sciences
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TSUCHIYA Koichiro
Department of Pharmacology, The University of Tokushima Graduate School of Medical Sciences
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Horinouchi Yuya
Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima
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Tajima Soichiro
Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima
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Hamano Shuichi
Department of Pathological Science and Technology, The Institute of Health Bioscience, The Universit
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Tamaki T
Department Of Pharmacology The Institute Of Health Bioscience The University Of Tokushima Graduate S
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YAMAGUCHI Kunihisa
Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate
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Tamaki Toshiaki
The Department Of Pharmacology Kagawa Medical School
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Tamaki Toshiaki
Department Of Pharmacology Kagawa Medical School
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Sugihara Takashi
Division Of Cardiovascular Medicine Tokushima University Hospital
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Ishizawa Keisuke
Department Of Pharmacology The Institute Of Health Bioscience The University Of Tokushima Graduate S
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Ishizawa Keisuke
Department Of Neurology Neurological Institute Tokyo Women's Medical College
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Tsuchiya Koichiro
Department Of Clinical Pharmacology Institute Of Health Biosciences The University Of Tokushima Grad
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Kanematsu Yasuhisa
Department Of Pharmacology Institute Of Health Biosciences The University Of Tokushima Graduate Scho
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Soeki Takeshi
Department Of Cardiovascular Medicine The University Of Tokushima
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Fukuhara Yayoi
Department Of Pharmacology The Institute Of Health Bioscience The University Of Tokushima Graduate S
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Hamano Shuichi
Department Of Pharmacology The Institute Of Health Bioscience The University Of Tokushima Graduate S
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Kawai Yoshichika
Dep. Of Pharmacology The Inst. Of Health Bioscience The Univ. Of Tokushima
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Kitaichi T
Department Of Cardiovascular Surgery The University Of Tokushima Graduate School Of Health Bioscienc
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Kitaichi T
Department Of Cardiovascular Surgery The University Of Tokushima Graduate School Of Health Bioscienc
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Takeichi Toshiaki
Department Of Internal Medicine Health Insurance Naruto Hospital
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Ishizawa Keisuke
Department Of Medical Pharmacology Institute Of Health Biosciences The University Of Tokushima Gradu
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Fukuhara Yayoi
Department Of Pharmacology Institute Of Health Biosciences The University Of Tokushima Graduate Scho
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Tajima Soichiro
Department Of Pharmacology Institute Of Health Biosciences The University Of Tokushima Graduate Scho
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Tsuchiya Koichiro
Department Of Cardiovascular Surgery The University Of Tokushima Graduate School Of Health Bioscienc
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Yamaguchi Kunihisa
Department of Food Science, Institute of Health Bioscience, The University of Tokushima Graduate School
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