Effect of eplerenone, enalapril and their combination treatment on diabetic nephropathy in type II diabetic rats

Young Sun Kang, Gang Jee Ko, Mi Hwa Lee, Hye Kyoung Song, Sang Youb Han, Kum Hyun Han, Hyoung Kyu Kim, Jee Young Han, Dae-Ryong Cha

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background. Recent data suggest that aldosterone antagonists have beneficial effects on diabetic nephropathy. In this study, we investigated the dose-dependent effect of eplerenone and a combined treatment with eplerenone and enalapril compared with each drug alone on renal function in type II diabetic rats. To further explore the molecular mechanism of action of combination therapy, we also performed in vitro study. Methods. The animals were divided into six groups as follows: normal control Long-Evans Tokushima Otsuka (LETO) rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, OLETF rats treated with low dose of eplerenone (50 mg/kg/day), OLETF rats treated with high dose of eplerenone (200 mg/kg/day), OLETF rats treated with enalapril (10 mg/kg/day) and OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and enalapril 10 mg/kg/day) for 6 months. Results. Treatment of OLETF rats had no significant effect on body weight, kidney weight and blood glucose levels. However, urinary albumin excretion, glomerular filtration rate and glomerulosclerosis were significantly improved in the enalapril group and improvement was observed in a dose-dependent manner in the eplerenone groups; the most dramatic decreases were observed in the combination group. In accordance with these findings, renal expressions of TGF-β1, type IV collagen and PAI-1 were also markedly decreased in the treatment groups, with the combined treatment providing the most significant level of improvement. In cultured mesangial cells, combined treatment resulted in an additive decrease in TGF-β1, PAI-1 and collagen gene expressions and protein production induced by high glucose and aldosterone stimulation. Conclusions. Aldosterone receptor antagonism provided additional benefits beyond blockade of the renin-angiotensin system in type II diabetic nephropathy.

Original languageEnglish
Pages (from-to)73-84
Number of pages12
JournalNephrology Dialysis Transplantation
Volume24
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

Fingerprint

Inbred OLETF Rats
Enalapril
Diabetic Nephropathies
Plasminogen Activator Inhibitor 1
Kidney
Mineralocorticoid Receptor Antagonists
Mineralocorticoid Receptors
Mesangial Cells
Drug Combinations
Renin-Angiotensin System
Collagen Type I
eplerenone
Aldosterone
Glomerular Filtration Rate
Blood Glucose
Albumins
Cultured Cells
Collagen
Body Weight
Gene Expression

Keywords

  • Albuminuria
  • Diabetic nephropathy
  • Enalapril
  • Eplerenone
  • Glomerulosclerosis

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Effect of eplerenone, enalapril and their combination treatment on diabetic nephropathy in type II diabetic rats. / Kang, Young Sun; Ko, Gang Jee; Lee, Mi Hwa; Song, Hye Kyoung; Han, Sang Youb; Han, Kum Hyun; Kim, Hyoung Kyu; Han, Jee Young; Cha, Dae-Ryong.

In: Nephrology Dialysis Transplantation, Vol. 24, No. 1, 01.01.2009, p. 73-84.

Research output: Contribution to journalArticle

Kang, Young Sun ; Ko, Gang Jee ; Lee, Mi Hwa ; Song, Hye Kyoung ; Han, Sang Youb ; Han, Kum Hyun ; Kim, Hyoung Kyu ; Han, Jee Young ; Cha, Dae-Ryong. / Effect of eplerenone, enalapril and their combination treatment on diabetic nephropathy in type II diabetic rats. In: Nephrology Dialysis Transplantation. 2009 ; Vol. 24, No. 1. pp. 73-84.
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AU - Han, Sang Youb

AU - Han, Kum Hyun

AU - Kim, Hyoung Kyu

AU - Han, Jee Young

AU - Cha, Dae-Ryong

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