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

Autor: Yang Huang, Dan, Boini, Krishna M., Osswald, Hartmut, Friedrich, Björn, Artunc, Ferruh, Ullrich, Susanne, Rajamanickam, Jeyaganesh, Palmada, Monica, Wulff, Peer, Kuhl, Dietmar, Vallon, Volker, Lang, Florian
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Zdroj: American Journal of Physiology: Renal Physiology; Dec2006, Vol. 291, pF1264-F1273, 10p, 1 Chart, 7 Graphs
Abstrakt: 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 NaCI 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% NaCI 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 NaCI 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 SGKI protects against the hypertensive effects of a combined high-fat/high-salt diet. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index