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

被引:60
作者
Huang, Dan Yang
Boini, Krishna M.
Osswald, Hartmut
Friedrich, Bjoern
Artunc, Ferruh
Ullrich, Susanne
Rajamanickam, Jeyaganesh
Palmada, Monica
Wulff, Peer
Kuhl, Dietmar
Vallon, Volker
Lang, Florian
机构
[1] Univ Tubingen, Dept Physiol, D-72076 Tubingen, Germany
[2] Univ Tubingen, Dept Pharmacol & Toxicol, D-72076 Tubingen, Germany
[3] Univ Tubingen, Dept Internal Med, D-72076 Tubingen, Germany
[4] Univ Hosp Neurol, Dept Clin Neurobiol, Heidelberg, Germany
[5] Free Univ Berlin, Dept Biol Chem & Pharm, D-1000 Berlin, Germany
[6] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[7] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[8] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA
关键词
insulin; blood pressure; aldosterone; mineralocorticoids; ENaC; kidney; EPITHELIAL SODIUM-CHANNEL; REGULATING FACTOR NHERF2; BLOOD-PRESSURE; INSULIN-RESISTANCE; COLLECTING DUCT; HORMONAL-REGULATION; PLASMA-MEMBRANE; PROTEIN-KINASE; NA+ TRANSPORT; UP-REGULATION;
D O I
10.1152/ajprenal.00299.2005
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:F1264 / F1273
页数:10
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