Effects of KD3-671, an Angiotensin II Type 1 Receptor Antagonist, on Anti-Thy-1 Nephritis in Rats
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概要
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We examined the effects of KD3-671 (2-propyl-8-oxo-1-[(2'-(H-tetrazole-5-yl)bipheny1-4-yl)methyl]-4,5,6,7-tetrahydrocycloheptimidazole), an angiotensin II type1 receptor antagonist, on an experimental rat model of mesangioproliferative glomerulonephritis, anti-Thy-1 nephritis. Anti-Thy-1 nephritis was induced by intravenous injection of 300μg/kg of anti-Thy-1.1 monoclonal antibody into rats. KD3-671 (3, 10, 30mg/kg per day) or enalapril (30mg/kg per day), an angiotensin II converting enzyme inhibitor, was given p.o. once daily from the day before the antibody injection (the 1st day) to the 15th day after. KD3-671 significantly inhibited an increase in the number of total and proliferating cell nuclear antigen-positive cells and the deposition of α-smooth muscle actin and fibronectin in the glomeruli of nephritic rats, but enalapril (30mg/kg per day) suppressed only the number of total cells and the deposition of α-smooth muscle actin in the glomeruli. Moreover, to elucidate the effect of KD3-671 on matrix deposition in the glomeruli, we measured the production of fibronectin in isolated glomeruli obtained from anti-Thy-1 nephritic rats. The glomeruli in anti-Thy-1 nephritic rats produced more fibronectin than that in control rats. KD3-671 (10^<-8>, 10^<-7>, 10^<-6>M) dose-dependently attenuated fibronectin production in isolated nephritic glomeruli. These findings suggest that KD3-671 may be an effective agent for the treatment of mesangioproliferative glomerulonephritis.
- 社団法人日本薬学会の論文
- 2003-06-01
著者
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Nagamatsu T
Department Of Pharmacobiology And Therapeutics Faculty Of Pharmacy Meijo University
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Nagamatsu Tadashi
名城大学 薬学部薬理学
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Nagamatsu Tadashi
Department Of Pharmacobiology And Therapeutics Faculty Of Pharmacy Meijo University
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Nagao T
Laboratory Of Pharmacobiology And Theraperutics Faculty Of Pharmaceutical Science Meijo University
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Nagao Toshiyuki
Department Of Pharmacology Faculty Of Pharmacy Meijo University
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Nagamatsu T
Department Of Pharmacology Faculty Of Pharmacy Meijo University
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Suzuki Y
School Of Pharmaceutical Sciences University Of Shizuoka
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Suzuki Y
Fukuoka Inst. Technol. Fukuoka
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鈴木 陽子
Meiji College Of Pharmacy
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OKA Tatsuya
Department of Pharmacology, Faculty of Pharmacy, Meijo University
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SUZUKI Yoshio
Department of Pharmacology, Faculty of Pharmacy, Meijo University
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Suzuki Y
Department Of Pharmacobiology And Therapeutics Faculty Of Pharmacy Meijo University
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Suzuki Y
Core Research For Evolutional Science And Technology (crest Jst) University Of Shizuoka School Of Ph
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Suzuki Y
Grad. Sch. Bioagric. Sci. Nagoya Univ.
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Oka T
Department Of Pharmacology Faculty Of Pharmacy Meijo University
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Suzuki Yoshio
Department Of Electronics Fukuoka Institute Of Technology
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Suzuki Y
Department Of Pharmacology Faculty Of Pharmacy Meijo University
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Suzuki Yoshio
Department Of Chemical Science & Technology Faculty Of Engineering Kyushu University
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