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Essigke, D. ; Kalo, M.Z.* ; Janessa, A.* ; Bohnert, B.N. ; Li, X.* ; Birkenfeld, A.L. ; Artunc, F.

Impact of aldosterone deficiency on the development of diuretic resistance in mice.

Pflugers Arch. 477, 827-840 (2025)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
The effect of diuretics can be limited by stimulation of counter-regulatory mechanisms, eventually leading to diuretic resistance. It is thought that the mineralocorticoid aldosterone might contribute to the development of diuretic resistance. To test this, we challenged genetically modified mice with or without a deletion of the gene coding for the aldosterone synthase (AS) with furosemide, hydrochlorothiazide (HCT) and triamterene. Urinary excretion was studied in metabolic cages; kidneys were studied for expression of sodium transporters. In both genotypes, a 4-day treatment with HCT via drinking water (400 mg/l) induced a similar natriuresis and modest loss of body weight < 10%. In contrast, furosemide (125 mg/l) and triamterene (200 mg/l) via drinking water stimulated a significantly higher natriuresis and body weight loss in AS-/- mice and in addition, triamterene caused massive hyperkalemia > 9 mM and acidosis (pH < 7.0). In AS+/+ mice, plasma aldosterone concentration tended to increase under furosemide and HCT administration, while triamterene induced a robust ~ sixfold increase. In the kidney, apical targeting and proteolytic activation of the epithelial sodium channel ENaC were stimulated in AS+/+ mice under triamterene treatment, an effect that was diminished in AS-/- mice. In conclusion, aldosterone is essentially involved in the development of diuretic resistance to ENaC blockade by triamterene and to a lesser extent to furosemide. In contrast, resistance to HCT was independent of aldosterone.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter (mesh): Aldosterone ; Aldosterone Synthase ; Diuretics ; Furosemide ; Hydrochlorothiazide ; Triamterene; Epithelial Sodium-channel; Gamma-enac; Cl-cotransporter; Na+; Expression; Homeostasis; Mechanisms; Serum; Mouse; Localization
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 0031-6768
e-ISSN 1432-2013
Zeitschrift Pflügers Archiv
Quellenangaben Band: 477, Heft: 6, Seiten: 827-840 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort Tiergartenstrasse 17, D-69121 Heidelberg, Germany
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502400-001
Förderungen Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Projekt DEAL
DOI 10.1007/s00424-025-03082-8
WOS ID 001465710900001
Scopus ID 105002355218
PubMed ID 40220064
Erfassungsdatum 2025-05-10
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