Systemic and local effects of angiotensin II blockade in experimental diabetic nephropathy

INTRODUCTION: Our objective was to evaluate the effect of blocking the renin-angiotensin system (RAS) on the expression of transforming growth factor-beta 1 (TGF-beta1), platelet derived growth factor-B (PDGF-B), tumour necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) in diabetic kidney glomeruli. MATERIALS AND METHOD: 1) Uninephrectomised streptozotocin induced diabetic rats were treated during eight months with vehicle (CD) or irbesartan (ID). Uninephrectomised non-diabetic rats were used as control group (ND). Protein urinary excretion and morphological renal damage were analysed. Glomerular expression of TGF-beta1, PDGF-B, VEGF and TNF-alpha were evaluated by Western blot and Immunohistochemistry. 2) Isolated glomeruli of diabetic rats were incubated 24-hours in the presence of different doses of irbesartan. Glomerular expression of TGF-beta1, PDGF-B, TNF-alpha and VEGF were determined by Western blot. RESULTS: ND and ID presented lower renal injury and proteinuria than CD (p<0.05). Glomerular expression of TGF-beta1, PDGF-B, TNF-alpha and VEGF were similar in ND and ID, but lower than in CD (p<0.05). In addition, in isolated diabetic rat glomeruli, irbesartan reduced the content of all these factors. CONCLUSION: Systemic and local administration of irbesartan lowers glomerular expression of TGF-beta1, PDGF-B, VEGF and TNF-alpha. These data suggest that part of the effect of lowering the expression of these growth factors and cytokines is due to a direct blockade of glomerular RAS.