期刊
NEPHROLOGY DIALYSIS TRANSPLANTATION
卷 24, 期 8, 页码 2338-2349出版社
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfp011
关键词
acute renal failure; aquaporin; iNOS; LPS; urine concentration
资金
- Danish National Research Foundation
- Danish Medical Research Council (ETBO)
- Korea Science and Engineering Foundation
- Ministry of Education, Science, and Technology [R01-2007-000-20441-0]
- National Research Foundation of Korea [R01-2007-000-20441-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 in-ducible 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 bothAQP2 and S256-phosphorylated AQP2 in CTX/OSOM and ISOM but not in inner medulla (IM). Thick ascending limb sodium transporters NIIE3 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.
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