Tempol Protects against Ischemic Acute Renal Failure by Inhibiting Renal Noradrenaline Overflow and Endothelin-1 Overproduction

• Fujii Toshihide

  Department of Pharmacology, Osaka University of Pharmaceutical Sciences

• Takaoka Masanori

  Department of Pharmacology, Osaka University of Pharmaceutical Sciences

• Ohkita Mamoru

  Department of Pharmacology, Osaka University of Pharmaceutical Sciences

• Matsumura Yasuo

  Department of Pharmacology, Osaka University of Pharmaceutical Sciences

抄録

The effects of tempol, a superoxide dismutase mimetic, on ischemia/reperfusion-induced acute renal failure (ARF), noradrenaline (NA) overflow and endothelin-1 (ET-1) overproduction in rats were examined. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal functional parameters such as blood urea nitrogen, plasma creatinine concentration, and fractional excretion of sodium, NA concentrations in renal venous plasma, and renal ET-1 contents were determined. Renal function in ARF rats markedly decreased at 1 d after reperfusion. Pre-ischemic treatment with tempol (10, 100 mg/kg, i.v.) dose-dependently attenuated 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, which were also significantly suppressed by the tempol treatment. There was a significant increase in NA concentrations in renal venous plasma after the ischemia/reperfusion, and this increase was markedly suppressed by the treatment with tempol. In addition, tempol treatment significantly attenuated the increment of ET-1 content in the kidney exposed to the ischemia/reperfusion. These findings suggest that tempol improves the post-ischemic renal injury by inhibiting the neural activity of renal sympathetic nerve and ET-1 overproduction.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 28 (4), 641-645, 2005

  公益社団法人 日本薬学会

キーワード

• ischemia
• acute renal failure
• tempol
• renal sympathetic nerve
• noradrenaline
• endothelin-1

詳細情報

• CRID: 1390282679602811904
• NII論文ID: 10016662131
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.28.641
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 7292396
• PubMed: 15802802
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7292396
• Web Site: http://www.jstage.jst.go.jp/article/bpb/28/4/28_4_641/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2006219550
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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