Protective Effect of SM-19712, a Novel and Potent Endothelin Converting Enzyme Inhibitor, on Ischemic Acute Renal Failure in Rats.
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- Matsumura Yasuo
- Department of Pharmacology,Osaka University of Pharmaceutical Sciences,Nasahara,Takatsuki,Osaka 569-1094,Japan
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- Kuro Toshihiko
- Department of Pharmacology,Osaka University of Pharmaceutical Sciences,Nasahara,Takatsuki,Osaka 569-1094,Japan
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- Kobayashi Yutaka
- Department of Pharmacology,Osaka University of Pharmaceutical Sciences,Nasahara,Takatsuki,Osaka 569-1094,Japan
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- Umekawa Kayo
- Researh Center,Sumitomo Pharmaceuticals Co.,Ltd.,Osaka 554-0022,Japan
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- Ohashi Naohito
- Researh Center,Sumitomo Pharmaceuticals Co.,Ltd.,Osaka 554-0022,Japan
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- Takaoka Masanori
- Department of Pharmacology,Osaka University of Pharmaceutical Sciences,Nasahara,Takatsuki,Osaka 569-1094,Japan
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抄録
Effects of SM−19712 {4−chloro−N−[[(4−cyano−3−methyl−1−phenyl−1H−pyrazol−5−yl)amino]carbonyl] benzenesulfonamide, monosodium salt}, a novel endothelin converting enzyme(ECE)inhibitor, on ischemic acute renal failure(ARF)in rats were examined in comparison with those of phosphoramidon, a conventional ECE inhibitor.ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy.Renal function in ARF rats markedly decreased at 24 h after reperfusion.Intravenous bolus injection of SM−19712(3, 10, 30 mg/kg)prior to the occlusion attenuated dose−dependently the ischemia/reperfusion−induced renal dysfunction.Histopathological examination of the kidney of ARF rats revealed severe renal damages such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, all of which were dose−dependently attenuated by SM−19712.Protective effects of phosphoramidon(10 mg/kg)on ARF−induced functional and tissue damages were less potent than that of the same dose of SM−19712.Endothelin−1(ET−1)content in the kidney after the ischemia/reperfusion was significantly increased, being the maximum level at 6 h after reperfusion, and this elevation was completely suppressed by the higher dose of SM−19712.Our findings support the view that renal ET−1 plays an important role in the development of ischemia/reperfusion−induced renal injury.SM−19712 may be useful in the treatment of ischemic ARF.
収録刊行物
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 84 (1), 16-24, 2000
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001204285216128
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- NII論文ID
- 10008184986
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- NII書誌ID
- AA00691188
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- COI
- 1:CAS:528:DC%2BD3cXmvVyruro%3D
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- ISSN
- 13473506
- 00215198
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- NDL書誌ID
- 5526009
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- PubMed
- 11043448
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- Web Site
- http://id.ndl.go.jp/bib/5526009
- https://ndlsearch.ndl.go.jp/books/R000000004-I5526009
- https://api.elsevier.com/content/article/PII:S0021519819305438?httpAccept=text/xml
- https://api.elsevier.com/content/article/PII:S0021519819305438?httpAccept=text/plain
- https://www.jstage.jst.go.jp/article/jjp/84/1/84_1_16/_pdf
- https://search.jamas.or.jp/link/ui/2001036367
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- 本文言語コード
- en
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- JaLC
- NDL
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