title: Resistance of mice lacking the serum- and glucocorticoid-inducible kinase SGK1 against salt-sensitive hypertension induced by a high-fat diet.
abstract: Mineralocorticoids enhance expression and insulin stimulates activity of the serum- and glucocorticoid-inducible kinase SGK1, which activates the renal epithelial Na+)channel (ENaC). Under a salt-deficient diet, SGK1 knockout mice (sgk1-/-) excrete significantly more NaCl than their wild-type littermates (sgk1+/+) and become hypotensive. The present experiments explored whether SGK1 participates in the hypertensive effects of a high-fat diet and high-salt intake. Renal SGK1 protein abundance of sgk1+/+ mice was significantly elevated after a high-fat diet. Under a control diet, fluid intake, blood pressure, urinary flow rate, and urinary Na+, K+, and Cl- excretion were similar in sgk1-/- and sgk1+/+ mice. Under a standard diet, high salt (1% NaCl in the drinking water for 25 days) increased fluid intake, urinary flow rate, and urinary Na+, K+, and Cl- excretion similarly in sgk1-/- and sgk1+/+ mice without significantly altering blood pressure. A high-fat diet alone (17 wk) did not significantly alter fluid intake, urinary flow rate, urinary Na+, K+, or Cl- excretion, or plasma aldosterone levels but increased plasma insulin, total cholesterol, triglyceride concentrations, and systolic blood pressure to the same extent in both genotypes. Additional salt intake (1% NaCl in the drinking water for 25 days) on top of a high-fat diet did not affect hyperinsulinemia or hyperlipidemia but increased fluid intake, urinary flow rate, and urinary NaCl excretion significantly more in sgk1-/- than in sgk1+/+ mice. Furthermore, in animals receiving a high-fat diet, additional salt intake increased blood pressure only in sgk1+/+ mice (to 132 +/- 3 mmHg) but not in sgk1-/- mice (120 +/- 4 mmHg). Thus lack of SGK1 protects against the hypertensive effects of a combined high-fat/high-salt diet.
authors.affiliation: Department of Pharmacology, University of Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
authors.forename: Dan Yang
authors.initials: DY
authors.lastname: Huang
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Boini
authors.forename: Hartmut
authors.initials: H
authors.lastname: Osswald
authors.forename: Björn
authors.initials: B
authors.lastname: Friedrich
authors.forename: Ferruh
authors.initials: F
authors.lastname: Artunc
authors.forename: Susanne
authors.initials: S
authors.lastname: Ullrich
authors.forename: Jeyaganesh
authors.initials: J
authors.lastname: Rajamanickam
authors.forename: Monica
authors.initials: M
authors.lastname: Palmada
authors.forename: Peer
authors.initials: P
authors.lastname: Wulff
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000450:Aldosterone / Q000097:blood; D000821:Animal Feed; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight; D004041:Dietary Fats / Q000494:pharmacology*; D004326:Drinking; D004435:Eating; D004573:Electrolytes / Q000097:blood; D005260:Female; D006977:Hypertension, Renal / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007003:Hypoglycemia / Q000378:metabolism / Q000503:physiopathology; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D014556:Urine; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000450:Aldosterone; D004041:Dietary Fats; D004573:Electrolytes; D017874:Immediate-Early Proteins; D007328:Insulin; D008055:Lipids; D017346:Protein Serine-Threonine Kinases; D017673:Sodium Chloride, Dietary; D000099184:Serum-Glucocorticoid Regulated Kinases