2024-03-29T15:18:53Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00019175
2023-11-16T05:22:07Z
499:508:509:1674
Roles of Oxidative Stress and the Mineralocorticoid Receptor in Cardiac Pathology in a Rat Model of Metabolic Syndrome
TAKAHASHI, KEIJI
56115
MURASE, TAMAYO
56116
TAKATSU, MIWA
56117
MATSUURA, NATSUMI
56118
NAGASAWA, KAI
56119
HATTORI, TAKUYA
56120
WATANABE, SHOGO
56121
MUROHARA, TOYOAKI
56122
NAGATA, KOHZO
56123
metabolic syndrome
cardiac remodeling
oxidative stress
mineralocorticoid receptor
renin-angiotensin-aldosterone system
2015-02
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.
departmental bulletin paper
Nagoya University School of Medicine
2015-02
Nagoya Journal of Medical Science
1-2
77
275
289
http://hdl.handle.net/2237/21281
2186-3326
0027-7622
eng
http://www.med.nagoya-u.ac.jp/medlib/nagoya_j_med_sci/7712.html