Dysregulation renaler Salztransporter in mit Gentamicin behandelten Ratten
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Philipps-Universität Marburg
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Abstract
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 80mg/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 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 (40mg/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.
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Dates
Created: 2012Issued: 2012-05-18Updated: 2012-06-08
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
NephrotoxizitätRenal magnesium wastingCalciumsensing Rezeptorrenaler MagnesiumverlustSodium transportSalztransportKonzentrationsdefektNKCC2Calciumsensing receptorNKCC2Concentrating defect
DFG-subjects
GentamicinNiereMagnesiumSalztransportNephrotoxizität
DDC-Numbers
610
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Sassen, Martin Christian (1021197653): Dysregulation renaler Salztransporter in mit Gentamicin behandelten Ratten. : Philipps-Universität Marburg 2012-05-18. DOI: https://doi.org/10.17192/z2012.0269.
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This item has been published with the following license: In Copyright