title: SGK1 as a determinant of kidney function and salt intake in response to mineralocorticoid excess.
abstract: 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 micromol.24 h(-1).g body wt(-1)) than in sgk1(-/-) mice (from 4 +/- 1 to 49 +/- 8 micromol.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.
authors: Dept. of Physiology, University of Tübingen, Gmelinstrasse 5, D-72076 Tübingen, Germany.
authors: Volker
authors: V
authors: Vallon
authors: Dan Yang
authors: DY
authors: Huang
authors: Florian
authors: F
authors: Grahammer
authors: Amanda W
authors: AW
authors: Wyatt
authors: Hartmut
authors: H
authors: Osswald
authors: Peer
authors: P
authors: Wulff
authors: Dietmar
authors: D
authors: Kuhl
authors: Florian
authors: F
authors: Lang
mesh_terms: D000818:Animals; D001066:Appetite / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003404:Creatinine / Q000378:metabolism; D003900:Desoxycorticosterone / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects; D005838:Genotype; D017874:Immediate-Early Proteins; D007668:Kidney / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008901:Mineralocorticoids / Q000378:metabolism*; D009318:Natriuresis / Q000187:drug effects; D009687:Nuclear Proteins / Q000172:deficiency / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000502:physiology*; D012965:Sodium Chloride / Q000008:administration & dosage* / Q000494:pharmacology; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D003404:Creatinine; D003900:Desoxycorticosterone; D017874:Immediate-Early Proteins; D008901:Mineralocorticoids; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D012965:Sodium Chloride; D000099184:Serum-Glucocorticoid Regulated Kinases