Roles of oxidative stress and the mineralocorticoid receptor in cardiac pathology in a rat model of metabolic syndrome

Keiji Takahashi, Tamayo Murase, Miwa Takatsu, Natsumi Matsuura, Kai Nagasawa, Takuya Hattori, Shogo Watanabe, Toyoaki Murohara, Kohzo Nagata

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Oxidative stress and the mineralocorticoid receptor (MR) are implicated in the pathogenesis of saltinduced left ventricular (LV) diastolic dysfunction associated with metabolic syndrome (MetS). We recently characterized DahlS.Z-Leprfa/Leprfa (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of MetS. We investigated the pathophysiological roles of increased oxidative stress and MR activation in cardiac injury with this model. DS/obese rats were treated with the antioxidant tempol (1 mmol/L in drinking water) or the selective MR antagonist eplerenone (15 mg/kg per day, per os) for 5 weeks beginning at 10 weeks of age. The increased systolic blood pressure and LV hypertrophy that develop in untreated DS/obese rats were substantially ameliorated by eplerenone but not by tempol. Eplerenone also attenuated LV fibrosis and diastolic dysfunction more effectively than did tempol in DS/obese rats, whereas cardiac oxidative stress and inflammation were reduced similarly by both drugs. Both the ratio of plasma aldosterone concentration to plasma renin activity and cardiac expression of the MR and serum/glucocorticoid-regulated kinase 1 genes were decreased to a greater extent by eplerenone than by tempol. Our results indicate that both increased oxidative stress and MR activation in the heart may contribute to the development of LV remodeling and diastolic dysfunction in DS/obese rats. The superior cardioprotective action of eplerenone is likely attributable to its greater antihypertensive effect, which is likely related to its greater inhibition of aldosterone-MR activity in the cardiovascular system.

Original languageEnglish
Pages (from-to)275-289
Number of pages15
JournalNagoya journal of medical science
Volume77
Issue number1-2
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • Cardiac remodeling
  • Metabolic syndrome
  • Mineralocorticoid receptor
  • Oxidative stress
  • Renin-angiotensin-aldosterone system

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Takahashi, K., Murase, T., Takatsu, M., Matsuura, N., Nagasawa, K., Hattori, T., Watanabe, S., Murohara, T., & Nagata, K. (2015). Roles of oxidative stress and the mineralocorticoid receptor in cardiac pathology in a rat model of metabolic syndrome. Nagoya journal of medical science, 77(1-2), 275-289.