title: Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency.
abstract: 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.
authors: Institutes of Anatomy and Physiology, and Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland;
authors: Abhijeet
authors: A
authors: Todkar
authors: Institutes of Anatomy and.
authors: Nicolas
authors: N
authors: Picard
authors: Institutes of Anatomy and.
authors: Dominique
authors: D
authors: Loffing-Cueni
authors: Institutes of Anatomy and.
authors: Mads V
authors: MV
authors: Sorensen
authors: Physiology, and.
authors: Marija
authors: M
authors: Mihailova
authors: Institute for Cellular and Molecular Physiology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany; and.
authors: Viatcheslav
authors: V
authors: Nesterov
authors: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors: Natalia
authors: N
authors: Makhanova
authors: Institute for Cellular and Molecular Physiology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany; and.
authors: Christoph
authors: C
authors: Korbmacher
authors: Physiology, and Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland;
authors: Carsten A
authors: CA
authors: Wagner
authors: Institutes of Anatomy and Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland; johannes.loffing@anatom.uzh.ch.
authors: Johannes
authors: J
authors: Loffing
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D019405:Cytochrome P-450 CYP11B2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006994:Hypoaldosteronism / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D017419:Potassium, Dietary / Q000494:pharmacology
chemical_list: D053503:Epithelial Sodium Channels; D015221:Potassium Channels; D017419:Potassium, Dietary; D000804:Angiotensin II; D019405:Cytochrome P-450 CYP11B2; D011188:Potassium
keywords: immunology; membranous nephropathy; pathology; pathophysiology renal disease; progression