Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency
| Autor: | Todkar, Abhijeet, Picard, Nicolas, Loffing-Cueni, Dominique, Sorensen, Mads V, Sørensen, Mads Vaarby, Mihailova, Marija, Nesterov, Viatcheslav, Makhanova, Natalia, Korbmacher, Christoph, Wagner, Carsten A, Loffing, Johannes |
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| Přispěvatelé: | University of Zurich, Loffing, Johannes |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Epithelial sodium channel Aldosterone synthase medicine.medical_specialty Potassium Channels 10017 Institute of Anatomy Hyperkalemia 030232 urology & nephrology 610 Medicine & health Kidney 10052 Institute of Physiology Mice 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Cytochrome P-450 CYP11B2 Homeostasis Epithelial Sodium Channels 030304 developmental biology Mice Knockout 0303 health sciences 2727 Nephrology biology Angiotensin II Potassium Dietary General Medicine medicine.disease Hypoaldosteronism Disease Models Animal Basic Research medicine.anatomical_structure Endocrinology Nephrology 10076 Center for Integrative Human Physiology Potassium biology.protein 570 Life sciences medicine.symptom Cotransporter |
| Zdroj: | Todkar, A, Picard, N, Loffing-Cueni, D, Sorensen, M V, Sørensen, M V, Mihailova, M, Nesterov, V, Makhanova, N, Korbmacher, C, Wagner, C A & Loffing, J 2014, ' Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency ', Journal of the American Society of Nephrology . https://doi.org/10.1681/ASN.2013111156 Journal of the American Society of Nephrology : JASN |
| DOI: | 10.1681/ASN.2013111156 |
| Popis: | Aldosterone-independent mechanisms may contribute to K(+) homeostasis. We studied aldosterone synthase knockout (AS(-/-)) mice to define renal control mechanisms of K(+) homeostasis in complete aldosterone deficiency. AS(-/-) mice were normokalemic and tolerated a physiologic dietary K(+) load (2% K(+), 2 days) without signs of illness, except some degree of polyuria. With supraphysiologic K(+) intake (5% K(+)), AS(-/-) mice decompensated and became hyperkalemic. High-K(+) diets induced upregulation of the renal outer medullary K(+) channel in AS(-/-) mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient to increase the electrochemical driving force for K(+) excretion was detected only with a 2% K(+) diet. Phosphorylation of the thiazide-sensitive NaCl cotransporter was consistently lower in AS(-/-) mice than in AS(+/+) mice and was downregulated in mice of both genotypes in response to increased K(+) intake. Inhibition of the angiotensin II type 1 receptor reduced renal creatinine clearance and apical ENaC localization, and caused severe hyperkalemia in AS(-/-) mice. In contrast with the kidney, the distal colon of AS(-/-) mice did not respond to dietary K(+) loading, as indicated by Ussing-type chamber experiments. Thus, renal adaptation to a physiologic, but not supraphysiologic, K(+) load can be achieved in aldosterone deficiency by aldosterone-independent activation of the renal outer medullary K(+) channel and ENaC, to which angiotensin II may contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive NaCl cotransporter may support renal adaptation by activation of flow-dependent K(+) secretion and increased intratubular availability of Na(+) that can be reabsorbed in exchange for K(+) secreted. |
| Databáze: | OpenAIRE |
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