Possible role of VEGF in the progression of kidney disease in streptozotocin (STZ)-induced diabetic rats: effects of an ACE inhibitor and an angiotensin II receptor antagonist

Horm Metab Res. 2004 Jul;36(7):458-64. doi: 10.1055/s-2004-825725.

Abstract

Two endothelium-derived factors, endothelin (ET), a vasoconstrictor, and vascular endothelial growth factor (VEGF), an angiogenic factor are thought to be involved in the pathogenesis of diabetic vascular complications. The aim of this study was to determine the effects of an angiotensin II type I (AT-1) receptor antagonist and an ACE inhibitor on the pathogenesis of VEGF and ET-1-mediated kidney disease in STZ-induced diabetic rats. Two days after STZ administration, diabetic rats were treated for 8 weeks with enalapril maleate, an ACE inhibitor, candesartan cilexetil, an AT-1 receptor antagonist, or saline. Urinary albumin and N-acetyl beta-D glucosaminidase (NAG) excretion as well as the VEGF protein content in the kidney were all found to be elevated in diabetic rats. Administration of enalapril maleate or candesartan cilexetil decreased the level of microalbuminuria and NAG excretion in diabetic rats. Administration of enalapril maleate also suppressed the elevated renal VEGF protein content in these animals while candesartan cilexetil treatment had no effect. Serum ET-1 and VEGF levels were unchanged by these treatments. These data support a role for AT-1 receptor antagonists and ACE inhibitors in the prevention of diabetic nephropathy, and suggest that the former may work by reducing renal VEGF levels.

Publication types

  • Comparative Study

MeSH terms

  • Albuminuria / etiology
  • Albuminuria / physiopathology
  • Analysis of Variance
  • Angiotensin Receptor Antagonists*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Benzimidazoles / pharmacology*
  • Biphenyl Compounds / pharmacology*
  • Blood Glucose / metabolism
  • Blotting, Western
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / prevention & control*
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / prevention & control*
  • Disease Progression
  • Enalapril / pharmacology*
  • Endothelin-1 / blood
  • Endothelin-1 / drug effects
  • Endothelin-1 / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Rats
  • Rats, Wistar
  • Streptozocin
  • Tetrazoles*
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / drug effects*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Blood Glucose
  • Endothelin-1
  • Tetrazoles
  • Vascular Endothelial Growth Factor A
  • Streptozocin
  • Enalapril
  • candesartan cilexetil