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Jørgen Frøkiær

AVP-induced increase in AQP2 and p-AQP2 is blunted in heart failure during cardiac remodeling and is associated with decreased AT1R abundance in rat kidney

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  • Sophie Constantin Lütken
  • ,
  • Jørgen Frøkiær
  • Søren Nielsen, Department of Health Science and Technology, Aalborg University, DK-9220 Aalborg Ø, Denmark

AIM: The objective was to examine the renal effects of long-term increased angiotensin II and vasopressin plasma levels in early-stage heart failure (HF). We investigated the regulations of the V2 vasopressin receptor, the type 1A angiotensin II receptor, the (pro)renin receptor, and the water channels AQP2, AQP1, AQP3, and AQP4 in the inner medulla of rat kidney.

METHODS: HF was induced by coronary artery ligation. Sixty-eight rats were allocated to six groups: Sham (N = 11), HF (N = 11), sodium restricted sham (N = 11), sodium restricted HF (N = 11), sodium restricted sham + DDAVP (N = 12), and sodium restricted HF + DDAVP (N = 12). 1-desamino-8-D-arginine vasopressin (0.5 ng h-1 for 7 days) or vehicle was administered. Pre- and post-treatment echocardiographic evaluation was performed. The rats were sacrificed at day 17 after surgery, before cardiac remodeling in rat is known to be completed.

RESULTS: HF rats on standard sodium diet and sodium restriction displayed biochemical markers of HF. These rats developed hyponatremia, hypo-osmolality, and decreased fractional excretion of sodium. Increase of AQP2 and p(Ser256)-AQP2 abundance in all HF groups was blunted compared with control groups even when infused with DDAVP and despite increased vasopressin V2 receptor and Gsα abundance. This was associated with decreased protein abundance of the AT1A receptor in HF groups vs. controls.

CONCLUSION: Early-stage HF is associated with blunted increase in AQP2 and p(Ser256)-AQP2 despite of hyponatremia, hypo-osmolality, and increased inner medullary vasopressin V2 receptor expression. Decreased type 1A angiotensin II receptor abundance likely plays a role in the transduction of these effects.

Original languageEnglish
JournalP L o S One
Volume10
Issue2
Pages (from-to)e0116501
ISSN1932-6203
DOIs
Publication statusPublished - 2015

    Research areas

  • Analysis of Variance, Angiotensin II, Animals, Aquaporin 2, Deamino Arginine Vasopressin, Echocardiography, Heart Failure, Immunoblotting, Immunohistochemistry, Kidney, Rats, Receptor, Angiotensin, Type 1, Receptors, Vasopressin, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't

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