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Jørgen Frøkiær

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

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  • Sophie Constantin Lütken, Denmark
  • Soo Wan Kim, Denmark
  • Thomas E N Jonassen, Denmark
  • David Marples, Denmark
  • Mark A Knepper, Denmark
  • Tae-Hwan Kwon, Denmark
  • Jørgen Frøkiær
  • Søren Nielsen, Denmark
  • Department of Anatomy
  • Biomedical Radio Isotope Techniques
Heart failure (HF) was induced by ligation of the left anterior descending artery (LAD). Left ventricular end diastolic pressure (LVEDP) greater than 25 mmHg (at day 23 after LAD ligation) was inclusion criterion. The rats were divided into three groups: Sham (n = 23, LVEDP: 5.6 +/- 0.6 mmHg); HF (n = 14, LVEDP: 29.4 +/- 1.4 mmHg), candesartan (1 mg/kg/day, s.c.) 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 AQP2 and pS256-AQP2 (p-AQP2) in HF. There was also markedly enhanced apical targeting of AQP2 and p-AQP2 in IMCD in HF compared to 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 the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) in kidneys from HF rats compared to sham: both effects were reversed or prevented by candesartan treatment. The protein abundance of alpha-ENaC was increased while beta-ENaC and gamma-ENaC expression was decreased in the cortex and outer stripe of the outer medulla in HF compared to sham, which were 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. Key words: collecting duct, heart failure, aquaporins, NHE3.
Original languageEnglish
JournalAmerican Journal of Physiology: Renal Physiology
Pages (from-to)1678-1688
Number of pages11
Publication statusPublished - 2009

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