Schmidt, Christoph and Hoecherl, Klaus and Schweda, Frank and Bucher, Michael (2007) Proinflammatory cytokines cause down-regulation of renal chloride entry pathways during sepsis. CRITICAL CARE MEDICINE, 35 (9). pp. 2110-2119. ISSN 0090-3493,
Full text not available from this repository. (Request a copy)Abstract
Objective. Sepsis is the most important trigger for acute renal failure, with tubular dysfunction and collapse in urine concentration. As chloride plays a major role in the urinary concentrating mechanisms, we aimed to investigate the regulation of renal chloride entry pathways, such as kidney-specific chloride channel 1, kidney-specific chloride channel 2, Barttin, thiazide-sensitive Na+-Cl- cotransporter, renal outer medullary potassium channel, and Na+/K+-adenosine triphosphatase during sepsis. Design: Prospective animal trial. Setting: Laboratory of the Department of Anesthesiology. Subjects: Male C57/BL6 and B6129SF2/J mice and mice deficient for tumor necrosis factor-alpha, interieukin-1-receptor-1, interferon-gamma, or interleukin-6. Interventions: Mice were injected with lipopolysaccharide (LPS) or proinflammatory cytokines. Hemodynamic and renal variables, cytokine concentrations, and expression of renal chloride-reabsorbing systems were investigated. Experiments with cytokine knockout mice, renal artery-clipped mice, and mice treated with glucocorticoids, low-dose LPS, and sodium nitroprusside were performed. Measurements and Main Results: LPS-injected mice presented with decreased blood pressure and glomerular filtration rate, increased fractional chloride excretion, and depressed expression of renal chloride transporters/channels. Similar alterations were observed after application of tumor necrosis factor-alpha, interleukin-1 beta, interferon-gamma, or interieukin-6. LPS-induced down-regulation of chloride transporters/channels was not affected in cytokine knockout mice. Glucocorticoid treatment inhibited LPS-induced increase of cytokine concentrations, diminished LPS-induced renal dysfunction, and attenuated the down-regulation of renal chloride transporters/channels, Injection of low-dose LPS increased renal tissue cytokines and down-regulated chloride entry pathways without arterial hypotension, indicating that renal ischemia due to systemic hypotension does not mediate down-regulation of renal chloride transporters/channels. In addition, renal ischemia induced by renal artery clipping or sodium nitroprusside administration did not influence chloride transporter/channel expression. Conclusions: Our results demonstrate down-regulation of renal chloride transporters/channels during sepsis, which is probably mediated by proinflammatory cytokines and accounts for the development of LPS-induced tubular dysfunction. Our findings contribute to the understanding, on one hand, the failure of single-anticytokine strategies and, on the other hand, the beneficial effects of glucocorticoids in the therapy of septic patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY RESPONSE SYNDROME; ROMK POTASSIUM CHANNEL; NITRIC-OXIDE SYNTHASE; CLC-K CHANNELS; SEPTIC SHOCK; RAT-KIDNEY; BARTTERS-SYNDROME; DOUBLE-BLIND; ACUTE ENDOTOXEMIA; DISTAL NEPHRON; lipopolysaccha ride; acute renal failure; cytokines; ischemia; glucocorticoids; chloride transporters/channels |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Dec 2020 08:51 |
| Last Modified: | 01 Dec 2020 08:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32240 |
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