Angiotensin II and Its Receptors in the Pathogenesis of Diabetic Nephropathy

  • David J. Leehey
  • Ashok K. Singh
  • Rekha Singh
Part of the Contemporary Diabetes book series (CDI)


Diabetic nephropathy (DN) is characterized by accumulation of extracellular matrix (ECM) in the kidney. Glomerular mesangial expansion and tubulo-interstitial fibrosis eventually leads to renal failure. The mediators of renal injury in this disease have not been fully identified. The peptide angiotensin (Ang) II has many hemodynamic and biochemical effects that could contribute to DN (Table 1). A prominent role for Ang II has been suggested by experimental and clinical evidence indicating that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have renoprotective effects and that these agents can attenuate the progression of glomerulosclerosis (1). In clinical studies, as well as studies conducted in experimental diabetic animals, it is difficult to separate hemodynamic from nonhemodynamic effects of Ang II. On the other hand, in vitro studies using cultured cells allow study of the specifically nonhemodynamic effects of Ang II and its inhibition (2). These nonhemodynamic effects of Ang II include stimulation of transforming growth factor (TGF)-β1, activation of matrix protein synthesis, and inhibition of matrix degradation (3,4). Ang II also increases generation of reactive oxygen species (ROS) in mesangial cells (MCs) (5) and may contribute to oxidant-induced renal injury.


Diabetic Nephropathy Mesangial Cell Nonproteolytic Activation Nonhemodynamic Effect Mesangial Cell Lysate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • David J. Leehey
    • 1
    • 2
  • Ashok K. Singh
    • 3
  • Rekha Singh
    • 4
  1. 1.Department of MedicineVeterans Affairs HospitalHines
  2. 2.Loyola University Stritch School of MedicineMaywood
  3. 3.Hektoen Institute for Medical ResearchChicago
  4. 4.Research ServiceVeterans Affairs HospitalHines

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