title: Dietary salt restriction activates mineralocorticoid receptor signaling in volume-overloaded heart failure.
abstract: Whether a high plasma aldosterone concentration induced by strict salt restriction promotes cardiac remodeling remains controversial. Male Sprague-Dawley rats at 10weeks of age were given normal salt (NS) (1.5% NaCl) or low salt (LS) (0.05% NaCl) diets. Each animal underwent aortocaval fistula creation for volume-overloaded heart failure or sham surgery. All rats with a fistula received either vehicle or a non-hypotensive dose of spironolactone (200mg/kg/day) by gavage. Two weeks later, the LS diet significantly increased the plasma aldosterone level in the sham-operated and fistula-created rats (2677+/-662pg/ml and 2406+/-422pg/ml) compared with that in rats given the NS diet (518+/-18pg/ml and 362+/-45pg/ml, respectively). In sham-operated rats, the difference in plasma aldosterone level did not affect the extent of myocardial fibrosis (1.8+/-0.1% with LS diet vs. 1.5+/-0.3% with NS diet). However, the increase in myocardial fibrosis in fistula-created rats was more prominent with the LS diet than with the NS diet (4.7+/-0.3% vs. 3.4+/-0.1%). In addition, the fistula-created rats on the LS diet expressed significantly increased oxidative stress and transforming growth factor-beta compared with those on the NS diets (P<0.05). These increases in the fistula-created rats on the LS diet were significantly suppressed by the non-hypotensive dose of spironolactone (P<0.05). These results suggest that increased plasma aldosterone level with strict salt restriction activated the mineralocorticoid receptor signaling in volume-overloaded condition, resulting in increased myocardial fibrosis.
authors.affiliation: Department of Internal Medicine III, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan. tatmori@poh.osaka-med.ac.jp
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Mori
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kurumazuka
authors.forename: Chika
authors.initials: C
authors.lastname: Matsumoto
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shirakawa
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kimura
authors.forename: Kento
authors.initials: K
authors.lastname: Kitada
authors.forename: Kana
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Matsuda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000450:Aldosterone / Q000097:blood*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001835:Body Weight; D048429:Cell Size; D000075202:Contraindications; D004039:Diet, Sodium-Restricted / Q000009:adverse effects*; D004719:Endomyocardial Fibrosis / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology*; D006439:Hemodynamics; D006973:Hypertension / Q000150:complications / Q000178:diet therapy*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D015398:Signal Transduction; D013148:Spironolactone / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D016212:Transforming Growth Factor beta; D020097:Natriuretic Peptide, Brain; D013148:Spironolactone; D014443:Tyrosine; D000450:Aldosterone; D009320:Atrial Natriuretic Factor