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WATER AND ELECTROLYTE HOMEOSTASIS

SGK1 as a determinant of kidney function and salt intake in response to mineralocorticoid excess

¹Department of Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany; ²Departments of Medicine and Pharmacology, University of California, San Diego, and Veterans Affairs San Diego Healthcare System, San Diego, California; ³Department of Physiology, University of Tübingen, Tübingen; ⁴Department of Clinical Neurobiology, University Hospital of Neurology, Heidelberg; and ⁵Department of Biology, Chemistry, and Pharmacy, Free University of Berlin, Berlin, Germany

Submitted 28 October 2004 ; accepted in final form 31 March 2005

Mineralocorticoids modify salt balance by both stimulating salt intake and inhibiting salt loss. Renal salt retention is accomplished by upregulation of reabsorption, an effect partially mediated by serum- and glucocorticoid-inducible kinase 1 (SGK1). The present study explored the contribution of SGK1 to the regulation of renal function, salt intake, and blood pressure during mineralocorticoid excess. DOCA/1% NaCl treatment increased blood pressure and creatinine clearance to a similar extent in SGK1-deficient sgk1^–/– and wild-type sgk1^+/+ mice but led to more pronounced increase of proteinuria in sgk1^+/+ mice (by 474 ± 89%) than in sgk1^–/– mice (by 154 ± 31%). DOCA/1% NaCl treatment led to significant increase of kidney weight (by 24%) and to hypokalemia (from 3.9 ± 0.1 to 2.7 ± 0.1 mmol/l) only in sgk1^+/+ mice. The treatment enhanced renal Na⁺ excretion significantly more in sgk1^+/+ mice (from 3 ± 1 to 134 ± 32 µmol·24 h^–1·g body wt^–1) than in sgk1^–/– mice (from 4 ± 1 to 49 ± 8 µmol·24 h^–1·g body wt^–1), pointing to SGK1-dependent stimulation of salt intake. With access to two drinking bottles containing 1% NaCl or water, DOCA treatment did not significantly affect water intake in either genotype but increased 1% NaCl intake in sgk1^+/+ mice (within 9 days from 3.5 ± 0.9 to 16.5 ± 2.4 ml/day) consistent with DOCA-induced salt appetite. This response was significantly attenuated in sgk1^–/– mice (from 2.6 ± 0.6 to 5.9 ± 0.9 ml/day). Thus SGK1 contributes to the stimulation of salt intake, kidney growth, proteinuria, and renal K⁺ excretion during mineralocorticoid excess.

aldosterone; salt appetite; proteinuria; potassium; mineralocorticoids; epithelial sodium channel

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