Dysregulation of renal sodium transporters in gentamicin-treated rats

M. C. Sassen, S. W. Kim, T. H. Kwon, M. A. Knepper, R. T. Miller, J. Frøkiær, S. Nielsen

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37 Scopus citations


We aimed to investigate the molecular mechanisms underlying the renal wasting of Na+, K+, Ca2+, and Mg2+ in gentamicin (GM)-treated rats. Male Wistar rats were injected with GM (40 or 80 mg/kg/day for 7 days, respectively; GM-40 or GM-80). The expression of NHE3, Na-K-ATPase, NKCC2, ROMK, NCC, α-, β- and γ-ENaC, and CaSR was examined in the kidney by immunoblotting and immunohistochemistry. Urinary fractional excretion of Na+, K+, Ca2+, and Mg2+ was increased and urinary concentration was decreased in both GM-40 and GM-80 rats. In cortex and outer stripe of outer medulla (cortex) in GM-80 rats, the expression of NHE3, Na-K-ATPase, and NKCC2 was decreased; NCC expression was unchanged; and CaSR was upregulated compared to controls. In the inner stripe of outer medulla (ISOM) in GM-80 rats, NKCC2 and Na-K-ATPase expression was decreased, whereas CaSR was upregulated, and NHE3 and ROMK expression remained unchanged. In GM-40 rats, NKCC2 expression was decreased in the cortex and ISOM, whereas NHE3, Na-K-ATPase, CaSR, ROMK, and NCC abundance was unchanged in both cortex and ISOM. Immunoperoxidase labeling confirmed decreased expression of NKCC2 in the thick ascending limb (TAL) in both GM-80- and GM-40-treated rats. Immunoblotting and immunohistochemical analysis revealed increased expression of α-, β-, and γ-ENaC in cortex in GM-80 rats, but not in GM-40 rats. These findings suggest that the decrease in NKCC2 in TAL seen in response to low-dose (40 mg/kg/day) gentamicin treatment may play an essential role for the increased urinary excretion of Mg2+ and Ca2+, and play a significant role for the development of the urinary concentrating defect, and increased urinary excretion of Na+ and K+. At high-dose gentamicin, both proximal and TAL sodium transporter downregulation is likely to contribute to this.

Original languageEnglish (US)
Pages (from-to)1026-1037
Number of pages12
JournalKidney international
Issue number6
StatePublished - Sep 2006


  • Calcium-sensing receptor
  • Concentrating defect
  • NKCC2
  • Nephrotoxicity
  • Renal magnesium wasting
  • Sodium transport

ASJC Scopus subject areas

  • Nephrology


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