Selective antagonism of ETA but not ETB receptor is protective against ischemic acute renal failure in rats

• Kuro Toshihiko

  Department of Pharmacology,Osaka University of Pharmaceutical Sciences,4-20-1 Nasahara,Takatsuki,Osaka 569-1094,Japan

• Kohnou Kaori

  Department of Pharmacology,Osaka University of Pharmaceutical Sciences,4-20-1 Nasahara,Takatsuki,Osaka 569-1094,Japan

• Kobayashi Yutaka

  Department of Pharmacology,Osaka University of Pharmaceutical Sciences,4-20-1 Nasahara,Takatsuki,Osaka 569-1094,Japan

• Takaoka Masanori

  Department of Pharmacology,Osaka University of Pharmaceutical Sciences,4-20-1 Nasahara,Takatsuki,Osaka 569-1094,Japan

• J. Opgenorth Terry

  Diabetes and Vascular Research Division,Abbott Laborratories,Abbott Park,IL 60064-6123,USA

• L. Wessale Jerry

  Diabetes and Vascular Research Division,Abbott Laborratories,Abbott Park,IL 60064-6123,USA

• Matsumura Yasuo

  Department of Pharmacology,Osaka University of Pharmaceutical Sciences,4-20-1 Nasahara,Takatsuki,Osaka 569-1094,Japan

書誌事項

タイトル別名

• Selective Antagonism of the ETA Receptor, but Not the ETB Receptor, Is Protective Against Ischemic Acute Renal Failure in Rats.

抄録

We investigated the effects of ABT-627, a selective ET_A-receptor antagonist, and A-192621, a selective ET_B-receptor antagonist, on ischemic acute renal failure(ARF)in rats.Ischemic ARF was induced by clamping the left renal artery and vein for 45min, 2 weeks after the contralateral nephrectomy.Renal function in untreated ARF rats markedly decreased at 24h after reperfusion and thereafter tended to recover gradually.ABT-627(1mg/kg, i.v.)administration before ischemia markedly attenuated the renal dysfunction induced by the ischemia/reperfusion, whereas A-192621(3mg/kg, i.v.)pretreatment was without effect.Histopathological examination of the kidney of untreated ARF rats revealed severe renal damage such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion.Histologically evident damage was improved by pretreatment with ABT-627, but not with A-192621.Daily oral administration of ABT-627(10mg/kg per day), but not A-192621(30mg/kg per day), given after the ischemia/reperfusion period also exerted protective effects.These findings clearly indicate that endothelin, acting via the ET_A receptor, participates in the pathogenesis of ischemic ARF.Thus, selective ET_A-receptor antagonism may be useful in the treatment of human ischemic ARF, whereas selective blockade of the ET_B receptor will probably be ineffective.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 82 (4), 307-316, 2000

  公益社団法人 日本薬理学会

キーワード

• Endothelin-1
• ET<SUB>A</SUB> receptor
• ET<SUB>B</SUB> receptor
• Acute renal failure
• Renal function

詳細情報

• CRID: 1390282679264453760
• NII論文ID: 10008183860
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.82.307
• COI: 1:CAS:528:DC%2BD3cXisl2gsL0%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL書誌ID: 5362759
• PubMed: 10875750
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5362759
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819306675?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819306675?httpAccept=text/plain
• Web Site: https://www.jstage.jst.go.jp/article/jjp/82/4/82_4_307/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2000199781
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
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