title: Salt excess causes left ventricular diastolic dysfunction in rats with metabolic disorder.
abstract: Metabolic syndrome is a highly predisposing condition for cardiovascular disease and could be a cause of excess salt-induced organ damage. Recently, several investigators have demonstrated that salt loading causes left ventricular diastolic dysfunction associated with increased oxidative stress and mineralocorticoid receptor activation. We, therefore, investigated whether excess salt induces cardiac diastolic dysfunction in metabolic syndrome via increased oxidative stress and upregulation of mineralocorticoid receptor signals. Thirteen-week-old spontaneously hypertensive rats and SHR/NDmcr-cps, the genetic model of metabolic syndrome, were fed a normal salt (0.5% NaCl) or high-salt (8% NaCl) diet for 4 weeks. In SHR/NDmcr-cps, salt loading induced severe hypertension, abnormal left ventricular relaxation, and perivascular fibrosis. Salt-loaded SHR/NDmcr-cps also exhibited overproduction of reactive oxygen species and upregulation of mineralocorticoid receptor-dependent gene expression, such as Na(+)/H(+) exchanger-1 and serum- and glucocorticoid-inducible kinase-1 in the cardiac tissue. However, in spontaneously hypertensive rats, salt loading did not cause these cardiac abnormalities despite a similar increase in blood pressure. An antioxidant, tempol, prevented salt-induced diastolic dysfunction, perivascular fibrosis, and upregulation of mineralocorticoid receptor signals in SHR/NDmcr-cps. Moreover, a selective mineralocorticoid receptor antagonist, eplerenone, prevented not only diastolic dysfunction but also overproduction of reactive oxygen species in salt-loaded SHR/NDmcr-cps. These results suggest that metabolic syndrome is a predisposed condition for salt-induced left ventricular diastolic dysfunction, possibly via increased oxidative stress and enhanced mineralocorticoid receptor signals.
authors.affiliation: Department of Nephrology and Endocrinology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Matsui
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ando
authors.forename: Hiroo
authors.initials: H
authors.lastname: Kawarazaki
authors.forename: Ai
authors.initials: A
authors.lastname: Nagae
authors.forename: Megumi
authors.initials: M
authors.lastname: Fujita
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shimosawa
authors.forename: Miki
authors.initials: M
authors.lastname: Nagase
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000450:Aldosterone / Q000097:blood; D000818:Animals; D001795:Blood Pressure Determination; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D000077545:Eplerenone; D054144:Heart Failure, Diastolic / Q000209:etiology / Q000503:physiopathology; D006334:Heart Function Tests; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000175:diagnosis*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012965:Sodium Chloride / Q000009:adverse effects* / Q000494:pharmacology; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D016482:Urinalysis; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology
chemical_list: D017382:Reactive Oxygen Species; D013148:Spironolactone; D012965:Sodium Chloride; D000450:Aldosterone; D000077545:Eplerenone