Dietary salt restriction activates mineralocorticoid receptor signaling in volume-overloaded heart failure

Mori, Tatsuhiko; Kurumazuka, Daisuke; Matsumoto, Chika; Shirakawa, Hisashi; Kimura, Sayaka; Kitada, Kento; Kobayashi, Kana; Matsuda, Hirohisa; Hayashi, Toshio; Kitaura, Yasushi; Matsumura, Yasuo

doi:10.1016/j.ejphar.2009.09.005

Cited by 17 publications

(18 citation statements)

References 28 publications

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“…Moreover, a low‐salt diet increases insulin resistance in humans . In addition, ResS impairs the endothelial effect of insulin and also enhances cardiac fibrosis in a rat model of heart failure . These results suggest that ResS may not always provide cardiometabolic benefits.…”

Section: Discussionmentioning

confidence: 99%

Combined Salt and Caloric Restrictions: Potential Adverse Outcomes

Homma

Huang

et al. 2017

JAHA

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BackgroundWe hypothesized that caloric restriction (CR) and salt restriction (ResS) would have similar effects on reducing cardiovascular risk markers and that combining CR and ResS would be synergistic in modulating these markers.Methods and ResultsTo test our hypothesis, rats were randomized into 2 groups: ad libitum liberal salt diet (ad libitum/high‐sodium, 1.6% sodium) or ResS diet (ad libitum/ResS, 0.03% sodium). CR was initiated in half of the rats in each group by reducing caloric intake to 60% while maintaining sodium intake constant (CR/high‐sodium, 2.7% sodium or CR/ResS, 0.05% sodium) for 4 weeks. CR in rats on a high‐sodium diet improved metabolic parameters, renal transforming growth factor‐β and collagen‐1α1 and increased plasma adiponectin and renal visfatin and NAD + protein levels. Although CR produced some beneficial cardiovascular effects (increased sodium excretion and reduced blood pressure), it also was associated with potentially adverse cardiovascular effects. Adrenal zona glomerulosa cell responsiveness and aldosterone levels and activation were inappropriately increased for the volume state of the rodent. Like CR on HS, CR on a ResS diet also produced relative increased zona glomerulosa responsiveness and an increased blood pressure with no improvement in metabolic parameters.ConclusionsThese results suggest that combining CR and ResS may decrease the beneficial effects of each alone. Furthermore, CR, regardless of dietary salt intake, inappropriately activates aldosterone production. Thus, caution should be used in combining ResS and CR because the combination may lead to increased cardiovascular risk.

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Section: Discussionmentioning

confidence: 99%

Combined Salt and Caloric Restrictions: Potential Adverse Outcomes

Homma

Huang

et al. 2017

JAHA

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“…However, the role of increased plasma aldosterone levels in the development of tissue damage is unclear. In an animal study, Mori et al showed that increased plasma aldosterone levels induced by a low-salt diet promoted myocardial fibrosis via MR in volume-overloaded rats [53]. Several clinical studies have claimed that reducing salt intake showed no effect or increased the risk of cardiovascular events [54], [55], [56]; however, significant controversy exists regarding this issue [57], [58], [59].…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress-Induced Glomerular Mineralocorticoid Receptor Activation Limits the Benefit of Salt Reduction in Dahl Salt-Sensitive Rats

et al. 2012

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BackgroundMineralocorticoid receptor (MR) antagonists attenuate renal injury in salt-sensitive hypertensive rats with low plasma aldosterone levels. We hypothesized that oxidative stress causes MR activation in high-salt-fed Dahl salt-sensitive rats. Furthermore, we determined if MR activation persisted and induced renal injury, even after switching from a high- to a normal-salt diet.Methods and FindingsHigh-salt feeding for 4 weeks increased dihydroethidium fluorescence (DHE, an oxidant production marker), p22phox (a NADPH oxidase subunit) and serum and glucocorticoid-regulated kinase-1 (SGK1, an MR transcript) in glomeruli, compared with normal-salt feeding, and these changes persisted 4 weeks after salt withdrawal. Tempol treatment (0.5 mmol/L) during high-salt feeding abolished the changes in DHE fluorescence, p22phox and SGK1. Dietary salt reduction after a 4-week high-salt diet decreased both blood pressure and proteinuria, but was associated with significantly higher proteinuria than in normal control rats at 4 weeks after salt reduction. Administration of tempol during high-salt feeding, or eplerenone, an MR antagonist (100 mg/kg/day), started after salt reduction, recovered proteinuria to normal levels at 4 weeks after salt reduction. Paraquat, a reactive oxygen species generator, enhanced MR transcriptional activity in cultured rat mesangial cells and mouse podocytes.ConclusionsThese results suggest that oxidative stress plays an important role in glomerular MR activation in Dahl salt-sensitive rats. Persistent MR activation even after reducing salt intake could limit the beneficial effects of salt restriction.

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“…They called for more studies to advance the understanding of the physiology of dietary sodium changes in HF and also the need for studies defining actions on symptoms and disease progression. Indeed, the findings of some studies suggest that excessive sodium restriction may be detrimental and result in excess cardiovascular morbidity and mortality, whereas moderate sodium intake may actually reduce hospitalizations and adverse outcomes . The modulating actions of dietary sodium in HF upon aldosterone to date remain undefined across the spectrum of ventricular systolic dysfunction, prompting the current study in experimental HF.…”

Section: Introductionmentioning

confidence: 99%

Dietary sodium modulation of aldosterone activation and renal function during the progression of experimental heart failure

Miller

Borgeson

Grantham

et al. 2014

European J of Heart Fail

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Aims Aldosterone activation is central to the sodium-fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Methods and Results Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: 1) high sodium [250 mEq (5.8 grams) per day, n=6]; 2) standard sodium [58 mEq (1.3 grams) per day, n=6]; and 3) sodium restriction [11 mEq (0.25 grams) per day, n=6]. During the 38 day study hemodynamics, renal function, renin activity (PRA), and aldosterone were measured. Changes in hemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups, however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Conclusions Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression.

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Dietary salt restriction activates mineralocorticoid receptor signaling in volume-overloaded heart failure

Cited by 17 publications

References 28 publications

Combined Salt and Caloric Restrictions: Potential Adverse Outcomes

Combined Salt and Caloric Restrictions: Potential Adverse Outcomes

Oxidative Stress-Induced Glomerular Mineralocorticoid Receptor Activation Limits the Benefit of Salt Reduction in Dahl Salt-Sensitive Rats

Dietary sodium modulation of aldosterone activation and renal function during the progression of experimental heart failure

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