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Am J Physiol Regul Integr Comp Physiol 292: R946-R954, 2007. First published October 5, 2006; doi:10.1152/ajpregu.00402.2006
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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in diastolic heart failure: beneficial effects of mineralocorticoid receptor blocker

Tomohito Ohtani,1,2 Miho Ohta,3 Kazuhiro Yamamoto,1 Toshiaki Mano,1,2 Yasushi Sakata,1 Mayu Nishio,1,2 Yasuharu Takeda,1,2 Junichi Yoshida,1,2 Takeshi Miwa,2 Mitsuhiro Okamoto,4 Tohru Masuyama,5 Yasuki Nonaka,6 and Masatsugu Hori1

1Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan; 2Genome Information Research Center, Osaka University, Suita, Japan; 3Laboratory of Nutrition, Koshien College, Nishinomiya, Japan; 4Department of Molecular Physiological Chemistry, Osaka University Graduate School of Medicine and 5Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan; and 6College of Nutrition, Koshien University, Takarazuka, Japan

Submitted 8 June 2006 ; accepted in final form 4 October 2006

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 by use of 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 wk (hypertensive DHF model) were divided at 13 wk into three groups: those treated with subdepressor doses of eplerenone (12.5 or 40 mg·kg–1·day–1) 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 levels 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 1,000 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, the myocardial aldosterone level increased in the DHF rats. However, its value was extremely low compared with 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.

diastole; heart failure; hypertension; ventricular function


Address for reprint requests and other correspondence: K. Yamamoto, Dept. of Cardiovascular Medicine, Osaka Univ. Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan (e-mail: kazuhiro{at}medone.med.osaka-u.ac.jp)




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