Effect of eplerenone, a selective aldosterone blocker, on the development of diabetic nephropathy in type 2 diabetic rats

Jae Hee Ahn, Ho Cheol Hong, Myong Jin Cho, Yoon Jung Kim, Hae Yoon Choi, Chai Ryoung Eun, Sae Jeong Yang, Hye-Jin Yoo, Hee Young Kim, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei-Hyun Baik, Dong Seop Choi, Nan Hee Kim

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)128-135
Number of pages8
JournalDiabetes and Metabolism Journal
Volume36
Issue number2
DOIs
Publication statusPublished - 2012 Apr 1

Fingerprint

Lisinopril
Inbred OLETF Rats
Diabetic Nephropathies
Aldosterone
Albumins
Mineralocorticoid Receptor Antagonists
Connective Tissue Growth Factor
Mineralocorticoid Receptors
Collagen Type IV
eplerenone
Plasminogen Activator Inhibitor 1
Transforming Growth Factors
Drug Combinations
Renin-Angiotensin System
Collagen Type I
Fibronectins
Angiotensin-Converting Enzyme Inhibitors
Kidney
Messenger RNA

Keywords

  • Aldosterone receptor blocker
  • Diabetic nephropathy
  • Eplerenone
  • Lisinopril
  • Type 2 diabetic rats

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Effect of eplerenone, a selective aldosterone blocker, on the development of diabetic nephropathy in type 2 diabetic rats. / 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.

In: Diabetes and Metabolism Journal, Vol. 36, No. 2, 01.04.2012, p. 128-135.

Research output: Contribution to journalArticle

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. / Effect of eplerenone, a selective aldosterone blocker, on the development of diabetic nephropathy in type 2 diabetic rats. In: Diabetes and Metabolism Journal. 2012 ; Vol. 36, No. 2. pp. 128-135.
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AU - Kim, Yoon Jung

AU - Choi, Hae Yoon

AU - Eun, Chai Ryoung

AU - Yang, Sae Jeong

AU - Yoo, Hye-Jin

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N2 - 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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