Abstract
The mechanism of salt-sensitive hypertension is not fully understood. Several studies point to a possible role of endothelin (ET)-1 in this form of hypertension. Serum-regulated and glucocorticoid-regulated kinase-1 (SGK1) mediates trafficking of the renal epithelial sodium channel. The aim of the study was to find out whether ET-1 regulates SGK1. Rat smooth muscle cells were incubated with ET-1 (10(-7) M, 0-120 minutes). After 30 minutes a significant increase in SGK1 mRNA was found (122 +/- 4.2%), and a maximum was reached after 120 minutes (217 +/- 7.6%). Incubation of smooth muscle cells with ET-1 (10(-7) mol/L) in the presence of an ETA receptor antagonist inhibited SGK1 gene transcription (93 +/- 3.7%). Western blot analysis showed a time-dependent increase in SGK1 protein in smooth muscle cells. These data indicate that ET-1 increases SKG1 mRNA and protein concentration. Inhibition of ET-1 by ET antagonism prevented a SGK1 increase. Therefore, ET antagonism might influence blood pressure by regulating the sodium balance through reducing SGK1 gene expression.
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