Angiotensin converting enzyme inhibitor suppresses glomerular transforming growth factor beta receptor expression in experimental diabetes in rats

Diabetologia. 2001 Apr;44(4):495-500. doi: 10.1007/s001250051648.


Aims/hypothesis: Activation of the renal transforming growth factor beta (TGF-beta) axis has been suggested to play a part in the development of diabetic nephropathy by a direct stimulatory effect of hyperglycaemia or through the activation of the renin-angiotensin system. Our aim was to evaluate the involvement of the renin-angiotensin system by examining the effects of ACE-inhibition on intrarenal changes in all three TGF-beta isoforms and receptors in experimental diabetes in vivo.

Methods: Immunocytochemistry, western blotting and ribonuclease protection assays were carried out for each TGF-beta isoform and receptor on kidney from non-diabetic and streptozotocin-diabetic rats after treatment with the ACE inhibitor, enalapril, for 30 days.

Results: Enalapril partially prevented the renal hypertrophy and fully prevented the increase in urinary albumin excretion rate in diabetic animals. The glomerular TGF-beta Type II Receptor mRNA and protein concentrations increased over 30 days in untreated diabetic animals compared with non-diabetic controls, while enalapril-treated diabetic animals showed a normalisation of TGF-beta Type II Receptor mRNA and protein.

Conclusion/interpretation: The ACE-inhibition had pronounced inhibitory effects on the increased expression of the glomerular TGF-beta Type II Receptor in the diabetic kidney required for intracellular signalling through this growth factor axis. This suggests a new mechanism of action of the ACE-inhibition in regulating the development of diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / prevention & control
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Blood Pressure
  • Body Weight
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Nephropathies / prevention & control
  • Enalapril / pharmacology
  • Enalapril / therapeutic use
  • Female
  • Gene Expression / drug effects*
  • Hypertrophy
  • Kidney / pathology
  • Kidney Glomerulus / chemistry*
  • Organ Size
  • Peptide Fragments / analysis
  • Procollagen / analysis
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Receptors, Transforming Growth Factor beta / analysis
  • Receptors, Transforming Growth Factor beta / genetics*


  • Angiotensin-Converting Enzyme Inhibitors
  • Peptide Fragments
  • Procollagen
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • procollagen type I carboxy terminal peptide
  • Enalapril