title: Effect of ramipril alone compared to ramipril with eplerenone on diabetic nephropathy in streptozocin-induced diabetic rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. thomas.mavrakanas@hcuge.ch
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mavrakanas
authors.forename: Angeliki
authors.initials: A
authors.lastname: Cheva
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kallaras
authors.forename: Georgios
authors.initials: G
authors.lastname: Karkavelas
authors.forename: Maria
authors.initials: M
authors.lastname: Mironidou-Tzouveleki
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003404:Creatinine / Q000097:blood / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood / Q000473:pathology / Q000517:prevention & control* / Q000652:urine; D004359:Drug Therapy, Combination; D000077545:Eplerenone; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D006984:Hypertrophy / Q000517:prevention & control; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D011507:Proteinuria / Q000517:prevention & control; D017257:Ramipril / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D003404:Creatinine; D017257:Ramipril