SGK1 as a determinant of kidney function and salt intake in response to mineralocorticoid excess.
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.
Vallon
Volker
V
Dept. of Physiology, University of Tübingen, Gmelinstrasse 5, D-72076 Tübingen, Germany.
Huang
Dan Yang
DY
Grahammer
Florian
F
Wyatt
Amanda W
AW
Osswald
Hartmut
H
Wulff
Peer
P
Kuhl
Dietmar
D
Lang
Florian
F
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
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