Schmidt, Christoph and Hoecherl, Klaus and Schweda, Frank and Kurtz, Armin and Bucher, Michael (2007) Regulation of renal sodium transporters during severe inflammation. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 18 (4). pp. 1072-1083. ISSN 1046-6673,
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Sepsis-associated acute renal failure. is characterized by decreased GFR and tubular dysfunction. The pathogenesis of endotoxemic tubular dysfunction with failure in urine concentration and increased fractional sodium excretion is poorly understood. This study investigated the regulation of renal sodium transporters during severe inflammation in vivo and in vitro. Injection of high-dosage LPS reduced BP and GFR, increased fractional sodium excretion, and strongly decreased the expression of Na+/H+-exchanger, renal outer medullary potassium channel, Na+-K+-2Cl(-) co-transporter, epithelial sodium channel, and Na+/K+-ATPase in mice. Also, injection of TNF-alpha, IL-1 beta, or IFN-gamma decreased renal function and expression of renal sodium transporters. LPS-induced downregulation of sodium transporters was not affected in cytokine-knockout mice. However, supplementary glucocorticoid treatment, which inhibited LPS-induced increase of tissue cytokine concentrations, attenuated LPS-induced renal dysfunction and downregulation of tubular sodium transporters. Injection of low-dosage LPS increased renal tissue cytokines and downregulated renal sodium transporters without arterial hypotension. In vitro, in cortical collecting duct cells, cytokines also decreased expression of renal outer medullary potassium channel, epithelial sodium channel, and Na+/K+-ATPase. Renal hypoperfusion by renal artery clipping did not influence renal sodium transporter expression, in contrast to renal ischemia-reperfusion injury, which depressed transporter expression. These findings demonstrate downregulation of renal sodium transporters that likely accounts for tubular dysfunction during inflammation. These data suggest that alteration of renal sodium transporters during LPS-induced acute renal failure is mediated by cytokines rather than renal ischemia. However, in a complex in vivo model of severe inflammation, the possible presence and influence of renal hypoperfusion and reperfusion on the expression of renal sodium transporters cannot be completely excluded.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COLLECTING DUCT CELLS; THICK ASCENDING LIMB; NITRIC-OXIDE SYNTHASE; NA+-K+-ATPASE; SEPTIC SHOCK; DOWN-REGULATION; DOUBLE-BLIND; DECREASED ABUNDANCE; SURFACE EXPRESSION; POTASSIUM CHANNEL; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie Biology, Preclinical Medicine > Institut für Physiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Dec 2020 06:28 |
| Last Modified: | 21 Dec 2020 06:28 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32976 |
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