Effects of ACE inhibition on the expression of type IV collagen and laminin in renal glomeruli in experimental diabetes

Acta Histochem. 2004;106(4):279-87. doi: 10.1016/j.acthis.2004.04.001.

Abstract

In the present study, we examined electron microscopically and immunohistochemically the effects of perindopril, an angiotensin-converting enzyme inhibitor, on renal microangiopathy in streptozotocin-induced diabetes in rats. To investigate changes in glomerular basement membrane (GBM) and tubular basement membrane components, we immunohistochemically localized type IV collagen and laminin. Animals have been divided into three groups of eight adult male rats each. The first group was the non-diabetic control group. The second group consisted of untreated diabetic rats. The third group consisted of diabetic rats that were treated with perindopril for 6 weeks. Blood glucose levels and body weight were measured. Morphometric analysis of kidney tissue was performed using light and electron microscopy to quantify glomerular size and thickness of the GBM. Blood glucose levels in diabetic rats were significantly increased when compared with non-diabetic controls. Blood glucose levels were not affected by perindopril treatment. Untreated diabetic rats showed increased glomerular size, thickening of the GBM and an increase in mesangial matrix as compared with controls. Treatment with perindopril prevented effectively glomerular hypertrophy and thickening of the GBM. Significant increase in type IV collagen and laminin was found in thickened GBM and mesangial matrix in kidneys of untreated diabetic rats. In perindopril-treated diabetic rats, staining of type IV collagen and laminin was less strong when compared with untreated diabetic rats. In conclusion, our data suggest that perindopril treatment is effective in preventing renal lesions possibly by ameliorating the diabetes-induced increase in expression of type IV collagen and laminin.

MeSH terms

  • Administration, Oral
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Basement Membrane / drug effects
  • Basement Membrane / metabolism
  • Basement Membrane / ultrastructure
  • Blood Glucose
  • Body Weight / drug effects
  • Collagen Type IV / metabolism*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / enzymology*
  • Diabetes Mellitus, Experimental / pathology
  • Fluorescent Antibody Technique, Indirect
  • Kidney Glomerulus / drug effects*
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / ultrastructure
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Laminin / metabolism*
  • Male
  • Perindopril / administration & dosage
  • Perindopril / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Blood Glucose
  • Collagen Type IV
  • Laminin
  • Perindopril