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This Article Full Text Full Text (PDF) All Versions of this Article: 297/6/F1678    most recent 00010.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lütken, S. C. Articles by Nielsen, S. PubMed PubMed Citation Articles by Lütken, S. C. Articles by Nielsen, S.

Changes of renal AQP2, ENaC, and NHE3 in experimentally induced heart failure: response to angiotensin II AT₁ receptor blockade

¹Water and Salt Research Center and ; ²Institute of Anatomy, University of Aarhus, Aarhus C, Denmark; ; ³Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea; ; ⁴Department of Pharmacology, Panum Institute, University of Copenhagen, Denmark; ; ⁵Institute of Membrane and Systems Biology, University of Leeds, Leeds, United Kingdom; ; ⁶Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; ; ⁷Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea; and ; ⁸Institute of Clinical Medicine, Aarhus University Hospital, Aarhus N, Denmark

Submitted January 7, 2009 ; accepted in final form September 8, 2009

Heart failure (HF) was induced by ligation of the left anterior descending artery (LAD). Left ventricular end-diastolic pressure (LVEDP) >25 mmHg (at day 23 after LAD ligation) was the inclusion criterion. The rats were divided into three groups: sham-operated (Sham, n = 23, LVEDP: 5.6 ± 0.6 mmHg), HF (n = 14, LVEDP: 29.4 ± 1.4 mmHg), and candesartan (1 mg·kg^–1·day^–1 sc)-treated HF (HF + Can, n = 9, LVEDP: 29.2 ± 1.2 mmHg). After 7 days (i.e., 29 days after LAD ligation) semiquantitative immunoblotting revealed increased abundance of inner medulla aquaporin-2 (AQP2) and AQP2 phosphorylated at Ser²⁵⁶ (p-AQP2) in HF. There was also markedly enhanced apical targeting of AQP2 and p-AQP2 in inner medullary collecting duct (IMCD) in HF compared with Sham rats, shown by immunocytochemistry. Candesartan treatment significantly reversed the increases in both AQP2 and p-AQP2 expression and targeting. In contrast, there were only modest changes in other collecting duct segments. Semiquantitative immunoblots revealed increased expression of type 3 Na⁺/H⁺ exchanger (NHE3) and Na⁺-K⁺-2Cl^– cotransporter (NKCC2) in kidneys from HF compared with Sham rats: both effects were reversed or prevented by candesartan treatment. The protein abundance of -epithelial sodium channel (-ENaC) was increased while β-ENaC and -ENaC expression was decreased in the cortex and outer stripe of the outer medulla in HF compared with Sham rats, which was partially reversed by candesartan treatment. These findings strongly support an important role of angiotensin II in the pathophysiology of renal water and sodium retention associated with HF.

collecting duct; aquaporin; type 3 Na⁺/H⁺ exchanger; Na⁺-K⁺-2Cl^– cotransporter; epithelial sodium channel