Impact of renal denervation on renal content of GLUT1, albuminuria and urinary TGF-β1, in streptozotocin-induced diabetic rats

in long-term diabetes mellitus, the progression of nephropathy has been related to the occurrence of autonomic neuropathy. This study was designed to evaluate the effects of bilateral denervation of the kidneys of streptozotocin-diabetic rats, an experimental model that presents diabetic nephropathy with increased abundance of cortical GLUT1 in the kidney and increased urinary excretion of albumin and transforming growth factor-beta1 (TGF-beta1). Twenty-four-hour urinary TGF-beta1 (ELISA), urinary albumin (electroimmunoassay) and GLUT1 protein levels (Western blotting) in the renal cortex and medulla were evaluated in diabetic (n = 13) and control (n = 13) rats 45 days after streptozotocin injection, submitted or not to surgical renal denervation. Evaluations were performed 15 days after the surgery. The effects of renal denervation were confirmed by intra-renal decrease of norepinephrine levels. Mean arterial pressure did not differ between diabetic and control rats, whether they underwent renal denervation or not. Renal denervation increased cortical (6905 +/- 287, 3506 +/- 193, 4144 +/- 246 and 5204 +/- 516 AU in renal-denervated controls, controls, renal-denervated diabetics and diabetics, respectively) and medullar GLUT1 protein in control rats, but reverted the cortical GLUT1 protein rise determined by diabetes. Although kidney denervation in diabetic rats induced a decrease in cortical GLUT1 abundance toward normal levels, these levels did not reach those of normal animals. However, renal denervation did not determine any changes in urinary albumin and urinary TGF-beta1 in both diabetic (127.3 +/- 12 mug/24 h and 111.8 +/- 24 ng mg(-1) creatinine, respectively) and control rats (45.9 +/- 3 mug/24 h and 13.4 +/- 4 ng mg(-1) creatinine, respectively). In conclusion, early-phase renal denervation, in streptozotocin-diabetic rats produces a normalisation of previously elevated cortical GLUT I protein content, but is not enough for reverting the increased urinary TGF-beta1 and albuminuria of diabetes. (C) 2003 Elsevier Science B.V. All rights reserved.