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1 Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan
2 Laboratory of Nutrition, Koshien College, Nishinomiya, Japan
3 Genome Information Research Center, Osaka University, Suita, Japan
4 Department of Molecular Physiological Chemistry, Osaka University Graduate School of Medicine, Suita, Japan
5 Cardiovascular Division, Hyogo College of Medicine, Nishinomiya, Japan
6 College of Nutrition, Koshien University, Takarazuka, Japan
* To whom correspondence should be addressed. E-mail: kazuhiro{at}medone.med.osaka-u.ac.jp.
Cardiac aldosterone levels have not been evaluated in diastolic heart failure (DHF), and its roles in this type of heart failure remain unclear. This study aimed to detect cardiac aldosterone using a liquid chromatographic mass spectrometric method and to assess the effects of mineralocorticoid receptor blockade on hypertensive DHF. Dahl salt-sensitive rats fed 8% NaCl diet from 7 weeks (hypertensive DHF model) were divided at 13 weeks into three groups; those treated with subdepressor doses of eplerenone (12.5, or 40 mg/kg/day) and an untreated group. Dahl salt-sensitive rats fed 0.3% NaCl diet served as controls. Cardiac aldosterone was detected in the DHF rats, but not in the control rats, with increased ventricular level of mineralocorticoid receptor. Cardiac levels of 11-deoxycorticosterone, corticosterone, and 11-dehydrocorticosterone were not different between the control and DHF rats, but the tissue level of corticosterone that has an affinity to mineralocorticoid receptor was 1000 times as high as that of aldosterone. Aldosterone synthase activity and CYP11B2 mRNA were undetectable in the ventricular tissue of the DHF rats. Administration of eplerenone attenuated ventricular hypertrophy, ventricular fibrosis, myocardial stiffening and relaxation abnormality, leading to the prevention of overt DHF. In summary, myocardial aldosterone level increased in the DHF rats. However, its value was extremely low as compared to corticosterone, and no evidence for enhancement of intrinsic myocardial aldosterone production was found. The upregulation of mineralocorticoid receptor may play a central role in the pathogenesis of DHF, and blockade of mineralocorticoid receptor is likely an effective therapeutic regimen of DHF.
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