Effect of ramipril alone compared to ramipril with eplerenone on diabetic nephropathy in streptozocin-induced diabetic rats.
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.
Mavrakanas
Thomas A
TA
First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. thomas.mavrakanas@hcuge.ch
Cheva
Angeliki
A
Kallaras
Konstantinos
K
Karkavelas
Georgios
G
Mironidou-Tzouveleki
Maria
M
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D003404:Creatinine; D017257:Ramipril