Effect of ramipril alone compared to ramipril with eplerenone on diabetic nephropathy in streptozocin-induced diabetic rats

Pharmacology. 2010;86(2):85-91. doi: 10.1159/000316113. Epub 2010 Aug 6.

Abstract

Background/aims: We studied the effect of the combined treatment with an angiotensin-converting enzyme (ACE) inhibitor (ramipril) and eplerenone compared with ramipril alone in streptozocin-induced diabetic rats.

Methods: Wistar rats were divided into 4 groups: nondiabetic controls, streptozocin-treated diabetic rats (50 mg/kg), diabetic rats receiving ramipril (1 mg/kg) and diabetic rats treated with the combination of ramipril (1 mg/kg) and eplerenone (100 mg/kg) for 8 weeks. Our model produced early-stage diabetic nephropathy.

Results: The diabetic rats developed polyuria, proteinuria, hyperfiltration (assessed by creatinine clearance) and histopathological evidence of renal injury including glomerular hypertrophy and mesangial expansion. Ramipril reduced proteinuria but its combination with eplerenone did not produce any greater benefit. Both treatment approaches prevented glomerular hypertrophy. Addition of eplerenone to ramipril prevented glomerular hyperfiltration.

Conclusion: Whether eplerenone should be used in addition to an ACE inhibitor or an angiotensin receptor blocker at an early stage of diabetic nephropathy remains questionable.

Publication types

  • Comparative Study

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Creatinine / blood
  • Creatinine / urine
  • Diabetes Mellitus, Experimental / complications*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / prevention & control*
  • Diabetic Nephropathies / urine
  • Drug Therapy, Combination
  • Eplerenone
  • Glomerular Mesangium / drug effects
  • Glomerular Mesangium / pathology
  • Hypertrophy / prevention & control
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiopathology
  • Male
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Proteinuria / prevention & control
  • Ramipril / therapeutic use*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Severity of Illness Index
  • Spironolactone / analogs & derivatives*
  • Spironolactone / therapeutic use

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone
  • Creatinine
  • Ramipril