Sodium-Induced Cardiac Aldosterone Synthesis Causes Cardiac Hypertrophy

Takeda, Yoshiyu; Yoneda, Takashi; Demura, Masashi; Miyamori, Isamu; Mabuchi, Hiroshi

doi:10.1210/endo.141.5.7529

Cited by 108 publications

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“…As demonstrated by Takeda et al (19), an increased activity and tissue synthesis of aldosterone was observed in normotensive rats fed a high-sodium diet for 8 wk after weaning. In addition, the mineralocorticoid receptor antagonist spironolactone was shown to prevent the development of left ventricular hypertrophy and fibrosis induced by 8-wk feeding of adult Wistar rats with an 8%-NaCl diet (9).…”

mentioning

confidence: 61%

“…At variance with Wistar (9), Wistar Kyoto, and spontaneously hypertensive rats (23), no clear enhancement of fibrosis was detected in the Sprague-Dawley rats, despite a longer duration of high sodium feeding. Although the circulating renin activity drastically fell during high sodium intake, an enhanced activity and expression of the renin-angiotensin system were reported in cardiac (8,19) and vascular tissue (12). On the contrary, a low-sodium diet entirely prevented the cardiac hypertrophy associated with chronic infusion of ANG II (14), thus suggesting a role for tissue ANG II in the response of the cardiovascular system to salt intake changes.…”

Section: Discussionmentioning

confidence: 98%

“…The prohypertrophic cardiac and vascular effects of high dietary sodium, independent of blood pressure, is well documented when the amount of sodium, as well as the duration of exposure, are large enough (10,13,14,19,23). At variance with Wistar (9), Wistar Kyoto, and spontaneously hypertensive rats (23), no clear enhancement of fibrosis was detected in the Sprague-Dawley rats, despite a longer duration of high sodium feeding.…”

Section: Discussionmentioning

confidence: 99%

“…*P Ͻ 0.05 vs. the NS group. decreased (6,19) while cardiac production of aldosterone and aldosterone synthase activity and expression (CYP11B2 mRNA) approximately doubled in response to high sodium intake in normotensive rats (19). In a study conducted in rats aged from 5-6 wk and fed an 8% NaCl diet for 4 or 8 wk, only the high dose (80 mg⅐kg Ϫ1 day Ϫ1 in drinking water) of spironolactone fully prevented left ventricular hypertrophy and fibrosis, as well as an increase in cardiomyocyte cross-sectional diameter (9).…”

Section: Discussionmentioning

confidence: 99%

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Cardiorenal abnormalities associated with high sodium intake: correction by spironolactone in rats

Cordaillat

Rugale

Casellas

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Cordaillat, Magali, Caroline Rugale, Daniel Casellas, Albert Mimran, and Bernard Jover. Cardiorenal abnormalities associated with high sodium intake: correction by spironolactone in rats. Am J Physiol Regul Integr Comp Physiol 289: R1137-R1143, 2005. First published May 26, 2005; doi:10.1152/ajpregu.00154.2005.-Reversal by the mineralocorticoid receptor antagonist spironolactone on cardiac and renal abnormalities, associated with long-term (since weaning) administration of a high (2 and 8% NaCl chow, HS2 and HS8) sodium diet, was assessed in Sprague-Dawley rats. At the age of 5 mo, spironolactone (20 or 100 mg/kg, gavage) or placebo were given for 14 days to HS2 and HS8 rats. A group fed a regular diet (0.8% NaCl, NS) remained untreated. High sodium intake had no detectable effect on blood pressure; however, cardiac mass index and cross-sectional area of the carotid artery, as well as albuminuria, were increased only in the HS8 group compared with the control group on NS diet. In addition, a marked reduction in glomerular filtration rate (by 40%), associated with a nonproportional fall in renal plasma flow (thus resulting in a decrease in filtration fraction), was observed only in the HS8 group. No change in cardiac and renal fibrosis was detected. Production of the reactive oxygen species (ROS) by aortic tissue was increased in HS8 rats, whereas ROS production by the heart was unaffected. Only the high dose of spironolactone was effective, as it markedly reversed the cardiac hypertrophy and renal hypofiltration associated with the HS8 feeding. The changes were observed in the absence of any effect on systemic blood pressure and production of ROS. These observations favor aldosterone's role in the deleterious effects of marked and prolonged increases in sodium intake. spironolactone; renal function; reactive oxygen species; cardiac hypertrophy IN ADDITION TO ITS WIDELY debated effect on blood pressure, chronic variation of sodium intake has been reported to modulate the cardiovascular morphology in human and experimental models. In animal studies, dietary sodium restriction has been shown to prevent the development of cardiac hypertrophy in renovascular (13) and ANG II-induced hypertension (14), independently of blood pressure. Reversal of cardiac hypertrophy was achieved by 6 wk on a low-sodium diet in 2-kidney, one-clip hypertensive rats (17). Administration of a diet containing 8% sodium chloride for more than 4 wk was associated with the development of left ventricular hypertrophy, cardiac fibrosis, and an increase in collagen content (10,23).Because an increase in systemic pressure associated with high sodium was not consistently observed, it was suggested that a direct effect of sodium may underlie the increased sensitivity of target organs to blood pressure. Interestingly, in a cohort of normotensive subjects and never-treated patients with essential hypertension, it was recently demonstrated that increasing dietary sodium (as estimated by 24-h natriuresis), enhanced the slope of the relationship between...

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confidence: 61%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Cardiorenal abnormalities associated with high sodium intake: correction by spironolactone in rats

Cordaillat

Rugale

Casellas

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Aldosterone blockers have been reported to suppress cardiac hypertrophy and cardiac fibrosis (27,28). Takeda et al reported that a high-salt intake accelerates the expression of the aldosterone synthase gene, CYP11B2 mRNA, in the cardiac tissues while also increasing cardiac aldosterone synthesis locally, which may affect cardiac hypertrophy independently of the RAAS in blood (29). Recently, Ye et al reported that the CYP11B2 and 11β-hydroxylase (CYP11B1) genes are not expressed in the rat heart (30).…”

Section: Discussionmentioning

confidence: 99%

Effects of Eplerenone and Salt Intake on Left Ventricular Remodeling after Myocardial Infarction in Rats

et al. 2006

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Eplerenone, a selective aldosterone blocker, has been shown to attenuate cardiac fibrosis and decrease cardiovascular events in both experimental and clinical studies. We examined the cardioprotective effect of eplerenone in myocardial infarction (MI) rats receiving different levels of salt in their diet. The MI rats were randomly divided into five groups: Group CL, animals received a low-salt diet (0.015%); Group EpL, a lowsalt diet with eplerenone (100 mg/kg/day in food); Group CH, a high-salt diet (0.9%); Group EpH, a high-salt diet with eplerenone; and Group C, a normal salt diet (0.3%). These diets were continued for 4 weeks.

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Cytochrome P450 enzymes and the heart

2009

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SummaryThe cytochrome P450 monooxygenase system (CYP) is a multigene superfamily of heme-thiolate enzymes, which are important in the metabolism of foreign and endogenous compounds. Genetic variations, drug interactions, or pathophysiological factors can lead to reduced, absent, or increased enzymatic activity. This altered CYP activity greatly influences an individual's response to therapeutic treatment. What is not known is the impact of these changes on the many functional roles of CYP in physiological and pathophysiological processes of the heart. Many extrahepatic tissues, like heart, contain active P450 enzymes but lack information regarding their role in cellular injury or homeostasis. Much of our current knowledge about cardiac CYP has been limited to studies investigating the role of fatty acid metabolites in heart. Traditional risk factors including diabetes, smoking, and hypertension have well established links to cardiovascular disease. And new evidence strongly suggests exposure to chemicals and other environmental agents has a profound impact on the cardiovascular system. These risk factors can independently affect the expression and activity of CYP enzymes. Therefore, altered CYP activity is important from a detoxification as well as a bioactivation perspective. Considering CYP, interactions are greatly dependent on inherited differences or acquired changes in enzyme activity further research into their potential impact on pathogenesis, risk assessment, and therapy of heart disease is warranted. This review explores the expression of CYP isoforms, their functional roles, and the effects of genetic variation in the heart.

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Sodium-Induced Cardiac Aldosterone Synthesis Causes Cardiac Hypertrophy

Cited by 108 publications

References 0 publications

Cardiorenal abnormalities associated with high sodium intake: correction by spironolactone in rats

Cardiorenal abnormalities associated with high sodium intake: correction by spironolactone in rats

Effects of Eplerenone and Salt Intake on Left Ventricular Remodeling after Myocardial Infarction in Rats

Cytochrome P450 enzymes and the heart

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