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

Abstract

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-β1), platelet derived growth factor-B (PDGF-B), tumour necrosis factor-alpha (TNF-α) 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-β1, PDGF-B, VEGF and TNF-α 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-β1, PDGF-B,TNF-α 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-β1, PDGF-B,TNF-α 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-β1, PDGF-B, VEGF and TNF-α. 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.