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This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/F1264    most recent 00299.2005v2 00299.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Huang, D. Y. Articles by Lang, F. Search for Related Content PubMed PubMed Citation Articles by Huang, D. Y. Articles by Lang, F.

Resistance of mice lacking the serum- and glucocorticoid-inducible kinase SGK1 against salt-sensitive hypertension induced by a high-fat diet

¹Departments of Pharmacology and Toxicology, ²Physiology, and ³Internal Medicine, University of Tübingen, Tübingen; ⁴Department of Clinical Neurobiology, University Hospital of Neurology, Heidelberg; ⁵Department of Biology, Chemistry, and Pharmacy, Free University Berlin, Berlin, Germany; and ⁶Departments of Medicine and Pharmacology, University of California, and Veterans Affairs San Diego Healthcare System, San Diego, California

Submitted 22 July 2005 ; accepted in final form 2 May 2006

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.

insulin; blood pressure; aldosterone; mineralocorticoids; ENaC; kidney

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