Objective: The serum and glucocorticoid-inducible kinase-1 (SGK1) has previously been shown to be highly expressed in renal injury such as glomerulonephritis and diabetic nephropathy. Inhibition of nitric oxide synthase with NG-nitro-L-arginine methyl ester (L-NAME) leads to arterial hypertension with subsequent renal injury. The present study explored whether chronic treatment with L-NAME affected renal SGK1 expression.
Methods: 36 Sprague-Dawley rats were divided into a control group and an experimental group, in which hypertension was induced by oral administration of L-NAME (100 mg/kg/day). The rats were sacrificed 4 and 8 weeks, respectively, after initiation of the treatment. Blood pressure was determined with the tail-cuff method, urinary albumin and beta2-microglobulin concentration were measured using an immunoturbidimetric assay, and SGK1 expression in renal cortex was quantified by real-time PCR and Western blotting.
Results: The administration of L-NAME increased systolic blood pressure significantly from 107 to 135 mm Hg within 4 weeks and to 155 mm Hg within 8 weeks. It further enhanced urinary excretion of albumin and beta2-microglobulin. Histology revealed marked fibrosis of glomerular and tubular tissue. The 4- and 8-week L-NAME treatment increased significantly (p < 0.01) SGK1 mRNA and protein abundance in renal cortex.
Conclusions: L-NAME treatment leads to hypertension, proteinuria and renal fibrosis. It increases renal transcription and expression of SGK1, which has previously been shown to foster matrix protein deposition and could thus contribute to renal injury.
Copyright 2006 S. Karger AG, Basel.