Endothelin-1 increases serum-glucocorticoid-regulated kinase-1 expression in smooth muscle cells.
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.
Wolf
Sabine C
SC
Medical Clinic III, Department of Cardiology, Hypertension and Renal Failure, University of Tuebingen, Germany. sabine.wolf@onlinehome.de
Schultze
Michael
M
Sauter
Gabriele
G
Risler
Teut
T
Brehm
Bernhard R
BR
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D002460:Cell Line; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044022:Receptor, Endothelin A / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D015854:Up-Regulation; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D001559:Benzhydryl Compounds; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D011743:Pyrimidines; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D000099184:Serum-Glucocorticoid Regulated Kinases; C405519:BSF 302146