Effect Of Dietary Sodium Restriction Research Articles

Aerobic Exercise Training Protects Against Insulin Resistance, Despite Low-Sodium Diet-Induced Increased Inflammation and Visceral Adiposity.

Dietary sodium restriction increases plasma triglycerides (TG) and total cholesterol (TC) concentrations as well as causing insulin resistance and stimulation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. Stimulation of the angiotensin II type-1 receptor (AT1) is associated with insulin resistance, inflammation, and the inhibition of adipogenesis. The current study investigated whether aerobic exercise training (AET) mitigates or inhibits the adverse effects of dietary sodium restriction on adiposity, inflammation, and insulin sensitivity in periepididymal adipose tissue. LDL receptor knockout mice were fed either a normal-sodium (NS; 1.27% NaCl) or a low-sodium (LS; 0.15% NaCl) diet and were either subjected to AET for 90 days or kept sedentary. Body mass, blood pressure (BP), hematocrit, plasma TC, TG, glucose and 24-hour urinary sodium (UNa) concentrations, insulin sensitivity, lipoprotein profile, histopathological analyses, and gene and protein expression were determined. The results were evaluated using two-way ANOVA. Differences were not observed in BP, hematocrit, diet consumption, and TC. The LS diet was found to enhance body mass, insulin resistance, plasma glucose, TG, LDL-C, and VLDL-TG and reduce UNa, HDL-C, and HDL-TG, showing a pro-atherogenic lipid profile. In periepididymal adipose tissue, the LS diet increased tissue mass, TG, TC, AT1 receptor, pro-inflammatory macro-phages contents, and the area of adipocytes; contrarily, the LS diet decreased anti-inflammatory macrophages, protein contents and the transcription of genes related to insulin sensitivity. The AET prevented insulin resistance, but did not protect against dyslipidemia, adipose tissue pro-inflammatory profile, increased tissue mass, AT1 receptor expression, TG, and TC induced by the LS diet.

Dietary Sodium Intake and Outcomes: a Secondary Analysis From Sodium-HF

This post hoc analysis of SODIUM-HF (Study of Dietary Intervention under 100 mmol in Heart Failure) assessed the association between baseline dietary sodium intake and change at 6 months with a composite of cardiovascular (CV) hospitalizations, emergency department visits and all-cause death at 12 and 24 months. Dietary sodium restriction is common advice for patients with heart failure (HF). Randomized clinical trials have not shown a beneficial effect of dietary sodium restriction on clinical outcomes. A multivariable Cox proportional hazard regression model was used to assess the association of dietary sodium intake measured at randomization with primary and secondary endpoints. The study included 792 participants. Baseline sodium intake was ≤ 1500 mg/day in 19.9% (n = 158), 1501-3000 mg/day in 56.5% (n = 448) and > 3000 mg/day in 23.4% (n = 186) of participants. The factors associated with higher baseline sodium intake were higher calorie consumption, higher body mass index and recruitment from Canada. Multivariable analyses showed no association between baseline sodium intake nor magnitude of 6-month change or 12- or 24-month outcomes. In a responder analysis, participants achieving a sodium intake < 1500 mg at 6 months showed an association with a decreased risk for the composite outcome (adjusted HR 0.52 [95% CI 0.25, 1.07] P = 0.08) and CV hospitalization (adjusted HR 0.51 [95% CI 0.24, 1.09] P = 0.08) at 12 months. There was no association between dietary sodium intake and clinical outcomes over 24 months in patients with HF. Responder analyses suggest the need for further investigation of the effects of sodium reduction in those who achieve the targeted dietary sodium-reduction level.

Dietary sodium intake and outcomes: a secondary analysis from SODIUM - HF

Abstract Background Sodium restriction is common advice provided to patients with heart failure, however, evidence from the SODIUM-HF trial and a subsequent meta-analysis failed to show a beneficial effect of dietary sodium restriction on outcomes. Purpose This secondary analysis of SODIUM HF is aimed to assess association between baseline dietary sodium intake, the change in dietary sodium at 6 months and a composite of cardiovascular hospitalization, emergency department visit, and all-cause death at 12 and 24 months. Methods Multivariable Cox proportional hazard regression model was used to assess association of dietary sodium level measured at randomization with primary and secondary endpoints. Adjusted Hazard ratios and 95% confidence intervals were presented. A responder analysis also explored the achieved dietary sodium at 6 months with subsequent risk for clinical outcomes. Results 792 participants were included. At baseline, sodium intake was ≤ 1500 mg/day in 19.9% (n = 158), &amp;gt;1500-3000 mg/day in 56.5% (n = 448) and &amp;gt;3000 mg/day in 23.4% (n= 186) of the participants. Women, older patients, and those with lower glomerular filtration rate and higher ejection fraction were more often represented in the group with sodium intake ≤1500 mg/day; conversely, diabetes, prior smoking, use of mineralocorticoid receptor antagonists, and ICD were observed in the groups of higher sodium intake levels (&amp;gt;3000 mg/day)(Table 1). Cox proportional hazard regression analysis showed no association between sodium level (per doubling) at baseline with clinical outcomes (all associations p=ns), however, adjusted models exhibited a trend towards a decreased risk of CV hospitalizations at 2 years. In the responder analysis, a trend towards a decreased adjusted risk for composite outcome and CV hospitalizations at 1 year in those achieving a sodium level &amp;lt;1500 mg at 6 months was observed (Table 2). Adjusted Cox proportional hazard regression analysis showed no association for 1- and 2-year outcomes per 500 mg increase in absolute difference in sodium level between baseline and 6 months. Conclusion In SODIUM HF, there was no association between sodium level at baseline with clinical outcomes at any time point but there is a trend towards a decreased risk of CV hospitalizations at 2 years and in patients achieving &amp;lt;1500 mg / day by 6 months, a trend towards fewer subsequent clinical events was present. This finding should be explored via a prospective clinical trial.Baseline characteristics of populationOutcomes

Effect of dietary sodium restriction on blood pressure in type 2 diabetes: A meta-analysis of randomized controlled trials

AimsAlthough current guidelines recommend reduction of salt intake in patients with diabetes, the benefits of reducing salt intake in people with type 2 diabetes mellitus (T2DM) lack clear evidence. Therefore, we performed a meta-analysis of available randomized controlled trials (RCTs) of sodium restriction and blood pressure (BP) in patients with T2DM. Data synthesisWe performed a systematic search of the online databases that evaluated the effect of dietary sodium restriction on BP in patients with T2DM. Sodium intake was expressed by 24 h urinary sodium excretion (UNaV). Q statistics and I2 were used to explore between-study heterogeneity. A random-effects model was used in the presence of significant heterogeneity; otherwise, a fixed-effects model was applied. Eight RCTs with 10 trials (7 cross-over and 3 parallel designs) were included in the meta-analysis. Compared with ordinary sodium intake, dietary sodium restriction significantly decreased UNaV (weighted mean difference, WMD: −38.430 mmol/24 h; 95% CI: −41.665 mmol/24 h to −35.194 mmol/24 h). Sodium restriction significantly lowered systolic BP (WMD: −5.574 mm Hg; 95% CI: −8.314 to −2.834 mm Hg; I2 = 0.0%) and diastolic BP (WMD: −1.675 mm Hg; 95% CI: −3.199 to −0.150 mm Hg; I2 = 0.0%) with low heterogeneity among the studies. No publication bias was found from Begg's and Egger's tests. ConclusionsSodium restriction significantly reduces SBP and DBP in patients with T2DM.

Effect of dietary sodium restriction on arterial stiffness: systematic review and meta-analysis of the randomized controlled trials.

Arterial stiffness is an independent cardiovascular risk factor and sodium intake could be a determinant of arterial stiffness. Nevertheless, the studies that investigated the effect of reducing dietary sodium intake on arterial stiffness in humans provided inconsistent results. Therefore, we performed a systematic review and a meta-analysis of the available randomized controlled trials of salt restriction and arterial stiffness to try and achieve more definitive conclusions. A systematic search of the online databases available (from 1996 through July 2017) was conducted including randomized controlled trials that reported arterial stiffness, expressed by carotid-femoral pulse wave velocity (PWV), as difference between the effects of two different sodium intake regimens. For each study, the mean difference and 95% confidence intervals were pooled using a random effect model. Sensitivity, heterogeneity, publication bias, subgroup and meta-regression analyses were performed. Eleven studies met the predefined inclusion criteria and provided 14 cohorts with 431 participants and 1-6 weeks intervention time. In the pooled analysis, an average reduction in sodium intake of 89.3 mmol/day was associated with a 2.84% (95% CI: 0.51-5.08) reduction in PWV. There was no significant heterogeneity among studies and no evidence of publication bias was detected. No single feature of the studies analyzed seemed to impact on the effect of salt restriction on PWV. The results of this meta-analysis indicate that restriction of dietary sodium intake reduces arterial stiffness. This effect seems be at least in part independent of the changes in blood pressure.

Salt in the diet in patients with heart failure: what to recommend.

Recognizing the relevance of sodium balance in heart failure, it has been presumed that patients with heart failure benefit from a low-sodium diet, though its efficacy and safety are unclear. The purpose of this review is to provide insight into the currently available evidence base for the effects of dietary sodium restriction in patients with chronic heart failure. There has been an increasing body of evidence on the effects of sodium restriction in heart failure; however, both observational and experimental studies have shown mixed results. Recent randomized controlled trial data has even suggested that sodium restriction may have detrimental effects in patients with heart failure. Only a few randomized controlled trials have included clinical outcomes as a primary endpoint. These have been either unpowered to test the association between reduced sodium intake and outcomes, or conducted in the context of an aggressive diuretic treatment and fluid restriction. The effects of a low-sodium diet on clinical outcomes in patients with heart failure remain unclear. Ongoing research into the effects of lowering sodium for patients with chronic or acute heart failure will shed light on the importance of holistic self-care and dietary strategies in heart failure.

Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial.

In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore studied the effects of dietary sodium restriction on BP and urinary albumin excretion (UAE) in kidney transplant recipients receiving RAAS blockade. Two-center randomized crossover trial. Stable outpatient kidney transplant recipients with creatinine clearance > 30mL/min, BP ≥120/80mmHg, receiving stable RAAS blockade therapy. 6-week regular-sodium diet (target, 150mmol/24 h) and a 6-week low-sodium diet (target, 50mmol/24 h). Main outcome parameters were systolic and diastolic BP, UAE, and estimated glomerular filtration rate (eGFR) at the end of each diet period. Dietary adherence was assessed by 24-hour urinary sodium excretion. We randomly assigned 23 kidney transplant recipients, of whom 22 (mean age, 58±8 [SD] years; 50% men; mean eGFR, 51±21mL/min/1.73m(2)) completed the study. One patient withdrew from the study because of concerns regarding orthostatic hypotension on the low-sodium diet. Sodium excretion decreased from 164±50mmol/24 h during the regular-sodium diet to 87±55mmol/24 h during the low-sodium diet (mean difference,-77 [95% CI,-110 to-44] mmol/24 h; P<0.001). Sodium restriction significantly reduced systolic BP from 140±14 to 129±12mmHg (mean difference,-11 [95% CI,-14 to-7] mmHg; P<0.001), diastolic BP from 86±8 to 79±8mmHg (mean difference,-7 [95% CI,-10 to-5] mmHg; P<0.001). We found no significant effect on natural log (ln)-transformed UAE (mean difference,-0.03 [95% CI,-0.6 to 0.6] ln(mg/24 h); P=0.9) or eGFR. No hard end points; small study; small proportion of patients willing to test the intervention; adherence to sodium diet was achieved in 86% of patients. In stable kidney transplant recipients receiving RAAS blockade, dietary sodium restriction effectively reduces BP without affecting eGFR. Dietary sodium restriction is relevant to BP management in kidney transplant recipients receiving RAAS blockade.

Effect of dietary sodium restriction on human urinary metabolomic profiles.

Metabolomics is a relatively new field of "-omics" research, focusing on high-throughput identification of small molecular weight metabolites. Diet has both acute and chronic effects on metabolic profiles; however, alterations in response to dietary sodium restriction (DSR) are completely unknown. The goal of this study was to explore changes in urine metabolites in response to DSR, as well as their association with previously reported improvements in vascular function with DSR. Using stored urine samples from a 10-week randomized placebo-controlled crossover study of DSR in 17 middle-aged/older adults (six men and 11 women; mean age 62±8 years) who had moderately elevated systolic BP (130-159 mmHg) and were otherwise healthy, a liquid chromatography/mass spectrometry-based analysis of 289 metabolites was performed. This study identified metabolites that were significantly altered between the typical (153±29 mmol/d) and low (70±29 mmol/d) sodium conditions, as well as their baseline (typical sodium) association with responsiveness to previously reported improvements in vascular endothelial function (brachial artery flow-mediated dilation) and large elastic artery stiffness (aortic pulse wave velocity). Of the 289 metabolites surveyed, 10 were significantly altered (nine were upregulated and one was downregulated) during the low sodium condition, and eight of these exceeded our prespecified clinically significant threshold of a >40% change. These metabolites were involved in biologic pathways broadly related to cardiovascular risk, nitric oxide production, oxidative stress, osmotic regulation, and metabolism. One metabolite, serine, was independently (positively) associated with previously reported improvements in the primary vascular outcome of brachial artery flow-mediated dilation. This proof-of-concept study provides the first evidence that DSR is a stimulus that induces significant changes in urinary metabolomic profiles. Moreover, serine was independently associated with corresponding changes in vascular endothelial function after DSR. Larger follow-up studies will be required to confirm and further elucidate the metabolic pathways that are altered in response to DSR.

The long-term effects of dietary sodium restriction on clinical outcomes in patients with heart failure. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure): A pilot study

To determine the feasibility of conducting a randomized controlled trial comparing a low-sodium to a moderate-sodium diet in heart failure (HF) patients. Patients with HF (New York Heart Association classes II-III) were randomized to low (1500 mg/d) or moderate-sodium (2300 mg/d) diet. Dietary intake was evaluated using 3-day food records. The end points were changes in quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores and B-type natriuretic peptide (BNP) levels from baseline to 6 months of follow-up presented as medians [25th, 75th percentiles]. Thirty-eight patients were enrolled (19/group). After 6 months, median sodium intake declined from 2137 to 1398 mg/d in the low-sodium and from 2678 to 1461 mg/d in the moderate-sodium diet group. Median BNP levels in the low-sodium diet group declined (216-71 pg/mL, P = .006), whereas in the moderate-sodium diet group, there was no change in BNP (171-188 pg/mL, P = .7; P = .17 between groups). For 6 months, median KCCQ clinical score increased in both groups (63-75 [P = .006] in the low-sodium diet group and 66-73 [P = .07] in the moderate-sodium group; P = .4 between groups). At 6 months, a post hoc analysis based on the dietary sodium intake achieved (> or ≤ 1,500 mg/d) in all patients showed an association between a sodium intake ≤ 1,500 mg/d and improvement in BNP levels and KCCQ scores. A dietary intervention restricting sodium intake was feasible, and achievement of this sodium goal was associated with lower BNP levels and improved quality of life in patients with HF.

Dietary sodium restriction: a neglected therapeutic opportunity in chronic kidney disease.

Restriction of dietary sodium is recommended at a population level as well as for groups at high cardiovascular risk, and chronic kidney disease (CKD). This review addresses recent evidence for the protective effect of dietary sodium restriction in CKD patients specifically. Sodium intake in CKD populations is generally high, and often above population average. Recent data demonstrated that moderately lower sodium intake in CKD patients is associated with substantially better long-term outcome of renin-angiotensin-aldosterone system (RAAS)-blockade, in diabetic and nondiabetic CKD, related to better effects of RAAS-blockade on proteinuria, independent of blood pressure. This is in line with better short-term efficacy of RAAS-blockade during moderate sodium restriction in diabetic and nondiabetic CKD. This effect of sodium restriction is likely mediated by its effects on volume status. Sustainable sodium restriction can be achieved by approaches on the basis of behavioral sciences. Moderate restriction of dietary sodium can substantially improve the protective effects of RAAS-blockade in CKD, by specific renal effects apparent from proteinuria reduction. The latter precludes straightforward extrapolation of data from nonrenal populations to CKD. Concerns regarding the adverse effects of a very low sodium intake should not distract from the protective effects of moderate sodium restriction. Prospective studies should assess the efficacy and sustainability of different strategies to target high sodium intake in CKD, along with measures at population level. http://links.lww.com/CONH/A14.

Low dietary sodium in diabetes nephropathy

In a meta-analysis that investigated the effects of dietary sodium restriction in diabetes nephropathy, although blood pressure fell, there were significant increases in plasma renin and aldosterone levels. In this article, we hypothesise that in diabetic nephropathy, ACE-I or ARB treatment attenuates any rise in RAS hormones that might result from dietary salt restriction and that the beneficial effects of the salt restriction such as a lower blood pressure outweigh any potentially negative consequences of RAS activation such as a rise in intraglomerular pressure because of the synergistic effects of sodium restriction and RAS antagonist therapy.

Sodium and Potassium and the Pathogenesis of Hypertension

The evidence relating blood pressure to salt intake in humans originates from population studies and randomized clinical trials of interventions on dietary salt intake. Estimates from meta-analyses of trials in normotensive subjects generally are similar to estimates derived from prospective population studies (+1.7-mm Hg increase in systolic blood pressure per 100 mmol increment in 24-hour urinary sodium). This estimate, however, does not translate into an increased risk of incident hypertension in subjects consuming a high-salt diet. The meta-analyses of intervention trials have consistently shown that potassium supplementation is associated with lowering of blood pressure. However, prospective studies relating health outcomes to 24-hour urinary sodium and/or potassium excretion produced inconsistent results. Taken together, available evidence does not support the current recommendations of a generalized and indiscriminate reduction of salt intake at the population level, although the blood-pressure lowering effect of dietary sodium restriction might be of value in hypertensive patients. Potassium supplementation in hypertensive patients or healthy persons is not recommended by the current guidelines, but importance of adhering to healthy diet rich in vegetables and fruits is emphasized.

Effect of dietary sodium restriction on body water, blood pressure, and inflammation in hemodialysis patients: a prospective randomized controlled study

Accumulating evidence suggests an association between body volume overload and inflammation in chronic kidney diseases. The purpose of this study was to evaluate the effect of dietary sodium reduction in body fluid volume, blood pressure (BP), and inflammatory state in hemodialysis (HD) patients. In this prospective controlled study, adult patients on HD for at least 90 days and those with C-reactive protein (CRP) levels ≥ 0.7 mg/dl were randomly allocated into two groups: group A, which included 21 patients treated with 2 g of sodium restriction on their habitual diet; and group B, which included 18 controls. Clinical, inflammatory, biochemical, hematological, and nutritional markers were assessed at baseline and after 8 and 16 weeks. Baseline characteristics were not significantly different between the groups. Group A showed a significant reduction in serum concentrations of CRP, tumor necrosis factor-α, and interleukin-6 during the study period, while BP and extracellular water (ECW) did not change. In group B, there were no changes in serum concentrations of inflammatory markers, BP, and ECW. Dietary sodium restriction is associated with the attenuation of the inflammatory state, without changes in BP and ECW, suggesting inhibition of a salt-induced inflammatory response.

The Effect of Sodium Restricted Diet on Plasma Visfatin Levels in Hypertensive Patients with Visceral Obesity

Aim/Background: Experimental and clinical studies revealed contradictory data concerning the influence of renin-angiotensin-aldosterone (RAA) system activation on visfatin release. The aim of the present study was the assessment of the effect of dietary sodium restriction with RAA system activation on visfatin level in hypertensive and normotensive patients with visceral obesity. Methods: The study included 24 hypertensive patients with visceral obesity (12 women) and 22 normotensive subjects with visceral obesity (11 women) constituting the control group. Plasma renin activity, plasma insulin, aldosterone and visfatin levels were determined twice, on normal-salt diet after 6-8 h in recumbent position and the second time after 3 days of dietary sodium restriction and upright position for 2 h. Dietary compliance was controlled by 24 h natriuresis measurement. Results: Hypertensive patients had significantly higher plasma visfatin level than the control group [11.0 (8.5-13.5) vs. 6.8 (6.0-7.6) ng/ml, p=0.003]. Dietary sodium restriction and upright position caused significant increase in PRA and plasma aldosterone level in both groups. While, plasma visfatin level remained unaffected. In the combined group plasma visfatin levels correlated with BMI (r=0.398), waist circumference (r=0.391), glucose (r=0.328), insulin (r=0.663), HOMA-IR (r=0.698), triglycerides (r=0.500) and CRP (r=0.546) but not with percentage of fat mass, percentage of trunk fat, and blood pressure values. Conclusions: 1) Increased plasma visfatin concentration may play a significant role in the pathogenesis of hypertension in patients with visceral obesity. 2) RAA system activation by dietary sodium restriction and upright position has no effect on plasma visfatin levels in subjects with visceral obesity.

Improving the efficacy of RAAS blockade in patients with chronic kidney disease

Reduction of blood pressure and proteinuria by blockade of the renin-angiotensin-aldosterone system (RAAS) has been the cornerstone of renoprotective intervention for patients with chronic kidney disease (CKD) for many years. Despite the proven efficacy of RAAS blockade, however, the reduction in proteinuria is insufficient in many patients, and does not prevent further deterioration of renal function. Short-term studies have shown that a variety of treatment intensification strategies have a beneficial effect on blood pressure and proteinuria, including RAAS blockade using either dose escalation or multiple drugs, and restriction of dietary sodium. Large clinical trials have shown that RAAS blockade with multiple drugs does not improve patients' long-term renal or cardiovascular outcome. By contrast, two post-hoc analyses of landmark trials in nephrology show beneficial renal and cardiovascular effects from avoiding excessive dietary sodium intake during single-agent RAAS blockade therapy. The effects of dietary sodium restriction on renal or cardiovascular outcome still require prospective confirmation. However, current data support the implementation of lifestyle changes to reduce dietary sodium intake in combination with single-agent RAAS blockade, rather than dual-agent RAAS blockade, as a potent and feasible strategy to mitigate the burden of renal and cardiovascular disease in patients with CKD.

The relevance of dietary sodium in hemodialysis

Since the earliest days of hemodialysis, dietary sodium restriction has been recommended as a therapeutic means to mitigate problems of extracellular volume overload, hypertension and inter-dialytic weight gain. Recently, there has been a proliferation of human subjects' research examining the potential effects of dietary sodium curtailment. Herein we examine the available evidence with respect to the effects of dietary sodium restriction on clinically relevant endpoints among hemodialysis patients.

Acute and chronic effects of dietary sodium restriction on renal tubulointerstitial fibrosis in cisplatin-treated rats

Renal interstitial fibrosis is a major complication of cisplatin (CP) treatment, and increased sodium intake may accelerate its progression by stimulating transforming growth factor (TGF)-β/Smad signaling. However, it is not clear whether a low-sodium diet has beneficial effects on the development of interstitial fibrosis because it activates the renin-angiotensin-aldosterone system. Here, we tested whether the TGF-β/Smad signaling pathway is stimulated in CP-treated rats, and whether the development of tubulointerstitial fibrosis in CP nephropathy can be checked by dietary sodium restriction. Male Sprague Dawley rats were randomly divided into controls, CP treatment and CP treatment with low-sodium diet. The acute experiment lasted 7 days with a single intraperitoneal injection (6 mg/kg) of CP, and the chronic experiment involved weekly injections (2 mg/kg) for 7 weeks. In both sets of experiments, CP treatment produced pronounced tubulointerstitial injury, increased infiltration of ED1-positive cells and increased expression of monocyte chemotactic protein-1 (MCP-1), α-smooth muscle actin (SMA), TGF-β1, phosphorylated Smad3, fibronectin and collagen III proteins. In the acute experiment, the increases in expression of osteopontin, MCP-1, α-SMA, TGF-β and collagen III were significantly reduced by dietary sodium restriction. In the chronic experiment, however, none of the measurements were improved by a low-sodium diet. Examination of CP-treated rat kidneys revealed de novo vimentin expression in tubular epithelial cells and invasion of α-SMA-positive tubular epithelial cells through the basement membrane into the interstitium. The pro-fibrotic effect of TGF-β in CP nephropathy appears to be associated with the epithelial-mesenchymal transition and is ameliorated by dietary sodium restriction only during the acute phase.

Dietary sodium intake regulates angiotensin II type 1, mineralocorticoid receptor, and associated signaling proteins in heart

Liberal or high-sodium (HS) intake, in conjunction with an activated renin-angiotensin-aldosterone system, increases cardiovascular (CV) damage. We tested the hypothesis that sodium intake regulates the type 1 angiotensin II receptor (AT(1)R), mineralocorticoid receptor (MR), and associated signaling pathways in heart tissue from healthy rodents. HS (1.6% Na(+)) and low-sodium (LS; 0.02% Na(+)) rat chow was fed to male healthy Wistar rats (n=7 animals per group). Protein levels were assessed by western blot and immunoprecipitation analysis. Fractionation studies showed that MR, AT(1)R, caveolin-3 (CAV-3), and CAV-1 were located in both cytoplasmic and membrane fractions. In healthy rats, consumption of an LS versus a HS diet led to decreased cardiac levels of AT(1)R and MR. Decreased sodium intake was also associated with decreased cardiac levels of CAV-1 and CAV-3, decreased immunoprecipitation of AT(1)R-CAV-3 and MR-CAV-3 complexes, but increased immunoprecipitation of AT(1)R/MR complexes. Furthermore, decreased sodium intake was associated with decreased cardiac extracellular signal-regulated kinase (ERK), phosphorylated ERK (pERK), and pERK/ERK ratio; increased cardiac striatin; decreased endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS), but increased peNOS/eNOS ratio; and decreased cardiac plasminogen activator inhibitor-1. Dietary sodium restriction has beneficial effects on the cardiac expression of factors associated with CV injury. These changes may play a role in the cardioprotective effects of dietary sodium restriction.

Sensitive periods for the effect of dietary sodium restriction on intact and denervated taste receptor cells.

Unilateral chorda tympani nerve (CT) section combined with dietary sodium restriction leads to striking alterations in sodium taste function. The regenerated rat CT exhibits deficits in sodium sensitivity, and surprisingly, there are also functional alterations in the intact, contralateral nerve. The studies presented here describe the functional "sensitive periods" for these aberrations and the number of taste buds present during corresponding stages. The regenerated CT is sensitive to dietary sodium restriction during the first 2 wk after denervation, whereas the intact CT is sensitive to dietary manipulation during the first week postsection. Therefore, distinct mechanisms are responsible for the effects of sodium restriction combined with denervation, because separate sensitive periods exist for the regenerated and intact CT nerves. Identification of mature taste buds with an antibody directed at anti-keratin 19 revealed that there is a loss of ~85% of taste buds on the denervated side of the tongue under control and low-sodium diets within the first week postsection. Thus, sodium restriction does not differentially affect the loss of taste buds following denervation.

Dietary sodium restriction restores nocturnal reduction of blood pressure in patients with primary aldosteronism.

The purpose of this study was to elucidate the effects of dietary sodium restriction on diurnal blood pressure (BP) variation in primary aldosteronism. We studied the diurnal variation in the systemic hemodynamic indices and in baroreflex sensitivity (BRS). In 13 subjects with aldosterone-producing adenomas (2 males; mean age, 39+/-2 years), intra-arterial pressure was monitored telemetrically on a normal salt diet (NaCl 10-12 g/day). Non-dippers were defined as those with a nocturnal reduction in systolic BP (SBP) of less than 10% of daytime SBP. Ten subjects showed a non-dipper pattern. Six of these "non-dippers" underwent repetitive hemodynamic studies on the last day of a 1-week low salt diet regimen (NaCl 2-4 g/day). Stroke volume was determined using Wesseling's pulse contour method, calibrated with indocyanine green dilution. BRS was calculated every 30 min as delta pulse interval/delta SBP on spontaneous variations. Nocturnal reduction of SBP was 4.1% on the normal salt diet. With sodium restriction, urinary sodium excretion decreased from 187+/-8 to 46+/-8 mmol/day, and body weight decreased from 57.9+/-2.1 to 56.6+/-1.9 kg. Night-time BP significantly decreased with dietary modification from 154+/-7/88+/-4 to 140+/-6/78+/-4 mmHg, whereas daytime BP was unaltered. With sodium restriction, cardiac index and stroke index decreased throughout the day. No significant difference was seen in either daytime or nighttime BRS between the two diets. We conclude that the non-dipper pattern is common in patients with an aldosterone-producing adenoma on a normal salt intake, and under such conditions, volume expansion appears to play a major role in the impairment of nocturnal BP reduction.