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Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion
Published on: May 26, 2022
Systemic and local effects of angiotensin II blockade in experimental diabetic nephropathy
Paula Vieitez1, Oscar Gómez, Esther R Uceda
1Endocrinology Department, Ramon y Cajal Hospital, Madrid, Spain.
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.
Insights
Blocking the renin-angiotensin system (RAS) with irbesartan reduced kidney damage and lowered expression of key growth factors in diabetic rats. This suggests a direct effect of irbesartan on glomerular RAS blockade.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetic kidney disease is characterized by increased expression of growth factors.
- The renin-angiotensin system (RAS) plays a crucial role in diabetic nephropathy progression.
Purpose of the Study:
- To investigate the impact of blocking the RAS on specific growth factors (TGF-β1, PDGF-B, TNF-α, VEGF) in diabetic kidney glomeruli.
- To determine if irbesartan has a direct effect on glomerular growth factor expression.
Main Methods:
- Streptozotocin-induced diabetic rats were treated with irbesartan or vehicle for eight months.
- Renal injury, proteinuria, and glomerular expression of TGF-β1, PDGF-B, TNF-α, and VEGF were assessed.
- Isolated glomeruli from diabetic rats were incubated with irbesartan to evaluate direct effects.
Main Results:
- Irbesartan treatment significantly reduced renal injury and proteinuria compared to controls.
- Glomerular expression of TGF-β1, PDGF-B, TNF-α, and VEGF was lower in irbesartan-treated diabetic rats.
- In isolated glomeruli, irbesartan directly reduced the content of these growth factors.
Conclusions:
- Systemic and local administration of irbesartan effectively lowers glomerular expression of TGF-β1, PDGF-B, VEGF, and TNF-α in diabetic kidneys.
- These findings indicate that direct blockade of the glomerular RAS contributes to irbesartan's renoprotective effects.
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