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

Am J Physiol Regul Integr Comp Physiol. 2005 Aug;289(2):R395-R401. doi: 10.1152/ajpregu.00731.2004.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetite / physiology*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Creatinine / metabolism
  • Desoxycorticosterone / pharmacology
  • Drinking / drug effects
  • Genotype
  • Immediate-Early Proteins
  • Kidney / physiology*
  • Mice
  • Mice, Knockout
  • Mineralocorticoids / metabolism*
  • Natriuresis / drug effects
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / physiology*
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / physiology*
  • Sodium Chloride / administration & dosage*
  • Sodium Chloride / pharmacology

Substances

  • Immediate-Early Proteins
  • Mineralocorticoids
  • Nuclear Proteins
  • Desoxycorticosterone
  • Sodium Chloride
  • Creatinine
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase