Selective Antagonism of the ET_A Receptor, but Not the ET_B Receptor, Is Protective Against Ischemic Acute Renal Failure in Rats

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We investigated the effects of ABT-627, a selective ET<SUB>A</SUB>-receptor antagonist, and A-192621, a selective ET<SUB>B</SUB>-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<SUB>A</SUB> receptor, participates in the pathogenesis of ischemic ARF.Thus, selective ET<SUB>A</SUB>-receptor antagonism may be useful in the treatment of human ischemic ARF, whereas selective blockade of the ET<SUB>B</SUB> receptor will probably be ineffective.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 82(4), 307-316, 2000-04-01

    公益社団法人 日本薬理学会

参考文献:  37件中 1-37件 を表示

被引用文献:  7件中 1-7件 を表示

各種コード

  • NII論文ID(NAID)
    10008183860
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    5362759
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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