Nicorandil, a K atp channel opener, alleviates chronic renal injury by targeting podocytes and macrophages

Yoshifuru Tamura, Katsuyuki Tanabe, Wataru Kitagawa, Shunya Uchida, George F. Schreiner, Richard J. Johnson, Takahiko Nakagawa

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Nicorandil exhibits a protective effect in the vascular system, which is thought to be due to vasodilatation from opening ATP-dependent potassium channels and donation of nitric oxide. Recently, nicorandil was shown to be renoprotective in models of acute kidney injury and glomerulone-phritis. However, the specific mechanisms of renoprotection are unclear. We evaluated the effect of nicorandil on the rat remnant kidney model of chronic kidney disease. Blood pressure was unchanged by a 10-wk course of nicorandil, while albuminuria was significantly reduced. Glomerular injury and tubulointerstitial injury were also ameliorated by nicorandil. Oxidative stress, as noted by renal nitrotyrosine level and urine 8-hydroxy-2′-deoxyguanosine, were elevated in this model and was significantly reduced by nic-orandil treatment. Treatment was associated with maintenance of the mitochondrial antioxidant, manganese SOD, in podocytes and with suppression of xanthine oxidase expression in infiltrating macro-phages. Interestingly, these two cell types express sulfonylurea receptor 2 (SUR2), a binding site of nicorandil in the ATP-dependent K channel. Consistently, we found that stimulating SUR2 with nic-orandil prevented angiotensin II-mediated upregulation of xanthine oxidase in the cultured macrophage, while xanthine oxidase expression was rather induced by blocking SUR2 with glibenclamide. In conclusion, nicorandil reduces albuminuria and ameliorates renal injury by blocking oxidative stress in chronic kidney disease.

Original languageEnglish
Pages (from-to)F339-F349
JournalAmerican Journal of Physiology - Renal Physiology
Volume303
Issue number3
DOIs
Publication statusPublished - Aug 1 2012
Externally publishedYes

Keywords

  • Manganese superoxide dismutase
  • Mitochondria
  • Oxidative stress
  • Xanthine oxidase

ASJC Scopus subject areas

  • Physiology
  • Urology

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