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KMID : 1200020120360020128
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Diabetes & Metabolism Journal
2012 Volume.36 No. 2 p.128 ~ p.135
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Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats
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Ahn Jae-Hee
Hong Ho-Cheol
Cho Myong-Jin
Kim Yoon-Jung
Choi Hae-Yoon
Eun Chai-Ryoung
Yang Sae-Jeong
Yoo Hye-Jin
Kim Hee-Young
Seo Ji-A
Kim Sin-Gon
Choi Kyung-Mook
Baik Sei-Hyun
Choi Dong-Seop
Kim Nan-Hee
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Abstract
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Background: Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats.
Methods: Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks.
Results: Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-β1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups.
Conclusion: Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.
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KEYWORD
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Aldosterone receptor blocker, Diabetic nephropathy, Eplerenone, Lisinopril, Type 2 diabetic rats
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