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NDT Advance Access originally published online on February 4, 2009
Nephrology Dialysis Transplantation 2009 24(8):2338-2349; doi:10.1093/ndt/gfp011
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Rapid and segmental specific dysregulation of AQP2, S256-pAQP2 and renal sodium transporters in rats with LPS-induced endotoxaemia

Emma T. B. Olesen1,2, Sophie de Seigneux1,3, Guixian Wang1,4, Sophie C. Lütken1,2, Jørgen Frøkiær1,4, Tae-Hwan Kwon1,5 and Søren Nielsen1,2

1 The Water and Salt Research Centre 2 Institute of Anatomy, University of Aarhus, Aarhus, Denmark 3 Service of Nephrology, Fondation pour Recherches Médicales, Genève, Switzerland 4 Institute of Clinical Medicine University of Aarhus, Aarhus, Denmark 5 Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea

Correspondence and offprint requests to: T.-H. Kwon; E-mail: thkwon{at}knu.ac.kr



  Abstract

Background. Acute renal failure (ARF) is a frequent complication of sepsis. Characteristics of ARF in sepsis are impaired urinary concentration, increased natriuresis and decreased glomerular filtration rate (GFR), in which inducible nitric oxide synthase (iNOS) has been revealed to play a role.

Aims. We aimed to investigate renal water and sodium excretion and in parallel the segmental regulation of renal AQP2 and major sodium transporters in rats with acute LPS-induced endotoxaemia. Next, we aimed to examine the changes of iNOS expression and activated macrophage infiltration in the kidney and the effects of iNOS inhibition on AQP2 and NKCC2 expression in LPS rats.

Methods. Rats were treated with LPS (i.p.) or with LPS + iNOS inhibitor L-NIL, and 6 h later kidneys were subjected to semiquantitative immunoblotting and immunohistochemistry.

Results. Polyuria and increased natriuresis were seen 6 h after LPS injection alongside downregulation of both AQP2 and S256-phosphorylated AQP2 in CTX/OSOM and ISOM but not in inner medulla (IM). Thick ascending limb sodium transporters NHE3 and NKCC2 were downregulated in ISOM and NaPi2 was decreased in CTX/OSOM, whereas NCC and ENaC were not consistently downregulated. Immunolabelling intensity of iNOS was increased in vascular structures and transitional epithelium, and an infiltration of activated macrophages was seen in CTX and ISOM. L-NIL co-treatment prevented the downregulation of NKCC2 but not AQP2 in LPS rats.

Conclusions. Early downregulation of AQP2 and sodium transporters takes place segmentally in the kidney after LPS administration. In addition, an infiltration of activated macrophages and increased iNOS expression may play a role in the urinary concentrating defect in acute LPS-induced entotoxaemia.

Keywords: acute renal failure; aquaporin; iNOS; LPS; urine concentration

Received for publication: 21. 1.08
Accepted in revised form: 6. 1.09


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