In:
Kidney and Blood Pressure Research, S. Karger AG, Vol. 32, No. 2 ( 2009), p. 119-127
Kurzfassung:
〈 i 〉 Background/Aims: 〈 /i 〉 Serum- and glucocorticoid-inducible kinase 1 (SGK1) stimulates the epithelial sodium channel (ENaC), renal outer medullary K 〈 sup 〉 + 〈 /sup 〉 channel 1, Na 〈 sup 〉 + 〈 /sup 〉 /K 〈 sup 〉 + 〈 /sup 〉 -ATPase and presumably the Na 〈 sup 〉 + 〈 /sup 〉 -Cl 〈 sup 〉 – 〈 /sup 〉 cotransporter (NCC). SGK1-deficient mice ( 〈 i 〉 sgk 〈 /i 〉 〈 sup 〉 –/– 〈 /sup 〉 ) show a compensated salt-losing phenotype with secondary hyperaldosteronism. The present experiments explored the role of SGK1 in the response to diuretics. 〈 i 〉 Methods: 〈 /i 〉 〈 i 〉 sgk1 〈 /i 〉 〈 sup 〉 –/– 〈 /sup 〉 mice and their wild-type littermates ( 〈 i 〉 sgk1 〈 /i 〉 〈 sup 〉 +/+ 〈 /sup 〉 ) were treated with the ENaC blocker triamterene (200 mg/l), the Na 〈 sup 〉 + 〈 /sup 〉 -K 〈 sup 〉 + 〈 /sup 〉 -2Cl 〈 sup 〉 – 〈 /sup 〉 cotransport inhibitor furosemide (125 mg/l), the NCC blocker hydrochlorothiazide (400 mg/l) and the mineralocorticoid receptor blocker canrenoate (800 mg/l) for 8 days. Renal SGK1 expression was studied using quantitative RT-PCR and immunofluorescence. 〈 i 〉 Results: 〈 /i 〉 Diuretic treatment increased SGK1 mRNA and protein expression in the kidney of wild-type 〈 i 〉 sgk1 〈 /i 〉 〈 sup 〉 +/+ 〈 /sup 〉 mice. The responses to furosemide, hydrochlorothiazide or canrenoate were not different between 〈 i 〉 sgk1 〈 /i 〉 〈 sup 〉 +/+ 〈 /sup 〉 and 〈 i 〉 sgk1 〈 /i 〉 〈 sup 〉 –/– 〈 /sup 〉 mice, and were accompanied by moderate increases in plasma aldosterone and urea concentrations. However, treatment with triamterene in 〈 i 〉 sgk1 〈 /i 〉 〈 sup 〉 –/– 〈 /sup 〉 mice (but not in 〈 i 〉 sgk1 〈 /i 〉 〈 sup 〉 +/+ 〈 /sup 〉 mice) led to severe, eventually lethal, body weight loss as well as increases in plasma aldosterone, urea and K 〈 sup 〉 + 〈 /sup 〉 concentrations. 〈 i 〉 Conclusions: 〈 /i 〉 SGK1 is required for diuretic tolerance to triamterene. The observations confirm the impaired kaliuretic potency of 〈 i 〉 sgk1 〈 /i 〉 〈 sup 〉 –/– 〈 /sup 〉 mice and point to a role of SGK1 in renal Na 〈 sup 〉 + 〈 /sup 〉 reabsorption by mechanisms other than ENaC.
Materialart:
Online-Ressource
ISSN:
1420-4096
,
1423-0143
Sprache:
Englisch
Verlag:
S. Karger AG
Publikationsdatum:
2009
ZDB Id:
1482922-8
