Sodium Restriction Research Articles

Protective Effects of Female Gut Microbiota Transplantation on Hypertension and Renal Damage in Male Dahl Salt-Sensitive Rats

We have previously demonstrated through microbiota transplantation studies that the gut microbiota importantly contributes to the development of hypertension, renal damage, and renal inflammation in the Dahl Salt-Sensitive (SS) rat fed a 4.0% NaCl high salt diet (HS). We also know that female SS rats are significantly protected from salt-induced hypertension, renal injury, and renal immune cell infiltration compared to males. One potential explanation for this sex difference is the substantial divergence we have observed in gut microbiota composition between male and female SS rats. Therefore, we hypothesized that gut microbiota transplantation between males and females would modulate the observed sex differences in salt-sensitivity. At 8 weeks of age, we first suppressed the native gut microbiota of male SS rat recipients via broad-spectrum antibiotics treatment (bacitracin and streptomycin, 2 g each/L, p.o.) for 3 days, followed by inoculation with either male or female donor cecal contents (oral gavage, 1 mL) for 7 consecutive days. Thus, our experimental groups are 1) male recipient rats repopulated with male donor microbiota (M+M, n=4) and 2) male recipient rats repopulated with female donor microbiota (M+F, n=3). Donor rats were maintained on the 0.4% NaCl low salt diet (LS) to more closely mimic the intrinsic microbiota of each sex. Telemeters were implanted at 10 weeks to allow for the continuous monitoring of blood pressure, followed by 3 weeks of HS challenge. At baseline, there were no differences in mean arterial pressure (MAP) between groups (123.4±1.3 vs 124.5±3.6 mmHg, M+M vs M+F on HS day 0, p=0.765). However, during the last week of HS challenge, males receiving female cecal microbiota transplantation had significantly reduced MAP compared to controls (153.6±3.4 vs 144.1±4.8 mmHg, M+M versus M+F on HS day 19, p=0.013). At the conclusion of the study, this reduction in blood pressure also coincided with a protection from renal damage, indicated by reduced urinary albumin excretion (209.0±37.1 vs 143.7±19.2 mg/day, M+M vs M+F, p=0.035), and an improvement in renal function, indicated by an increase in creatinine clearance (0.36±0.02 vs 0.48±0.01 ml/min/g kidney, M+M vs M+F, p=0.002). However, there appeared to be no effects on renal inflammation, with no changes to either the circulating or renal immune cell profile between rats receiving male or female microbiota. Furthermore, in female SS rat recipients that were subsequently transplanted with either male or female donor cecal contents, we observed no significant effects related to sex of donor microbiota in terms of blood pressure, renal damage, or renal inflammation. Together, these data demonstrate the anti-hypertensive and renoprotective effects of the female gut microbiota to recipient male SS rats. Moreover, there are additional factors within the female host that appear to be protective against the male microbiota. 19CDA34660184, HL161231 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Input from afferent renal nerves is involved in progression of hypertensive heart failure through central vasopressin-mediated sympathoexcitation

Introduction: Paraventricular nucleus of hypothalamus (PVN), a control center of sympathetic outflow, receives the input from afferent renal nerves. Although acute stimulation of afferent renal nerves increases central sympathetic outflow, it remains unclear if the renal afferents contribute to progression of heart failure. Acute stimulation of afferent renal nerves was reported to increase plasma vasopressin concentration. In addition, central dendritic release of vasopressin by activation of vasopressin-expressing neurons located in the PVN may cause sympathoexcitation via stimulation of neighboring presympathetic neurons in the PVN. Therefore, we hypothesized that the chronic input from afferent renal nerves contributes to sympathoexcitation and hypertensive cardiac dysfunction along with activation of vasopressin-expressing neurons and presympathetic neurons in the PVN. Methods: Male Dahl salt-sensitive rats were fed low salt diet (LS) or 8% high salt diet from 6 weeks of age, and the high salt-fed rats were allocated to selective afferent renal denervation (HS-ARDN) or sham surgery (HS-Sham) at 9 weeks. The effect of ARDN on central sympathetic regulation was investigated at 12 weeks (pre-heart failure phase). In another cohort, its effect on cardiac phenotypes was evaluated at 16 weeks (heart failure phase). Results: At 12 weeks, plasma norepinephrine level was increased in HS-Sham compared to LS and was attenuated by ARDN (LS 188.7±16.5 pg/ml, HS-Sham 563.8±82.7 pg/ml, HS-ARDN 327.4±50.2 pg/ml; n=15, 12, 14; p<0.05). The c-Fos expression, a marker of neuronal activity, in presympathetic neurons in the PVN was also increased in HS-Sham and attenuated in HS-ARDN, which was in parallel with the c-Fos expression in vasopressin-expressing neurons in the PVN. At 16 weeks, the decrease of left ventricular (LV) fractional shortening (HS-Sham 25.9±1.7 % vs LS 46.7±0.6 %, n=9, 9; p<0.01) was improved in HS-ARDN (42.2±1.2 %, n=7; p<0.01 vs HS-Sham). LV weight and lung weight were significantly increased in HS-Sham compared to LS (LV weight/body weight: 4.39±0.19 mg/g vs 2.53±0.03 mg/g; lung weight/body weight: 5.29±0.37 mg/g vs 3.55±0.05 mg/g; p<0.05), and these changes were attenuated in HS-ARDN (LV weight/body weight: 3.73±0.14 mg/g; lung weight/body weight: 4.17±0.11 mg/g; p<0.05 vs HS-Sham). Histological LV fibrosis and fibrosis marker expression, such as connective tissue growth factor, in LV were significantly attenuated in HS-ARDN compared to HS-Sham. ARDN did not significantly impact the high salt-induced blood pressure elevation in both cohorts. Conclusion: The input from afferent renal nerves contributes to cardiac dysfunction, probably via the central vasopressin-mediated sympathoexcitation even without blood pressure changes in hypertensive heart failure model. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Efficacy of an Educational Intervention for Sodium Restriction in Patients with Hypertension: A Randomized Controlled Trial

There is sound evidence showing the efficacy of non-pharmacological interventions in lowering blood pressure (BP); however, adherence is usually poor. Interventions to induce behavioral changes aim to improve the ability to read labels, choose foods, and eat low-sodium meals, reinforcing adherence to sodium restriction. In this randomized parallel-controlled trial, we assessed the effectiveness of an educational intervention using the Dietary Sodium Restriction Questionnaire (DSRQ) scores. A follow-up period of 6 months was conducted. Participants were randomized into (1) an educational intervention provided by a registered dietitian on individual visits and dietary planning; (2) a control group with the usual care and dietary recommendations. Patients underwent 24-h ambulatory BP monitoring, 12-h fasting blood tests, spot urine collection, and assessment using DSRQ. We randomized 120 participants (67.5% women and 68.3% Caucasians), and 25 participants were lost to follow-up. The 24-h sodium urinary excretion changed in the control (Δ −1610 mg/day; 95% confidence interval [CI] −1800 to −1410) and intervention groups (Δ −1670 mg/day; 95% CI −1800 to −1450) over time. There was no significant difference in the 24-h estimated sodium between groups. In hypertensive patients, DSRQ-based educational intervention is effective for improving the ability to detect and overcome obstacles to a low-sodium restriction diet but is as effective as dietary recommendations for lowering sodium.

Salty taste test for a low-salt diet to control blood pressure

BackgroundReducing salt intake helps prevent complications of cerebrovascular disease. To help patients accept a low-sodium diet, the salty taste test is used to evaluate how much salt an individual actually consumes. The aim of this study was to help patients with hypertension reduce their salt intake by helping them recognize the difference between their subjective perception of saltiness and the objective test results.MethodsWe enrolled workers who visited a local occupational health institution in the period from April to August 2019. Demographic and physical characteristics were recorded. Blood pressure measurement and use of medication were also recorded. A questionnaire was used to investigate whether people liked or disliked salty food, i.e., preference for saltiness, and whether they usually ate salty, normal, or fresh food, i.e., the subjective perception of saltiness. Subsequently, the taste determination kit provided by the Ministry of Food and Drug Safety was used to objectively test saltiness at various salty taste concentrations. The Ministry of Food and Drug Safety program (No. 10-093760) was used as the salty taste judgment tool.ResultsA total of 86 workers were surveyed. Eleven of 18 workers (61.1%) who reported usually eating fresh food actually ate normal or salty food. Thirteen of 37 workers (35.1%) who reported eating normal food actually ate salty food. Thirteen of 31 workers (41.9%) who reported eating salty food actually ate fresh or normal food. Of 46 workers who reported disliking salty food, 14 (30.4%) actually ate salty food, while 20 (43.5%) ate normal food. The subjective perception and preference for saltiness were not significantly correlated with the objective test results (P = ​​0.085 and P = 0.110, respectively). As for the subjective perception and preference for saltiness, Cohen’s weighted kappa for the taste judgment result were 0.23 and 0.22, respectively, indicating a low degree of agreement.ConclusionsIn dietary counseling to prevent cerebrovascular and cardiovascular diseases, rather than relying on the subjective perception of saltiness, a salty taste test should be performed such that people can recognize their salty food eating habits through objective evaluation.

The Role of Nitric Oxide in the Micro- and Macrovascular Response to a 7-Day High-Salt Diet in Healthy Individuals.

This study aimed to investigate the specific role of nitric oxide (NO) in micro- and macrovascular response to a 7-day high-salt (HS) diet, specifically by measuring skin microvascular local thermal hyperemia and the flow-mediated dilation of the brachial artery, as well as serum NO and three NO synthase enzyme (NOS) isoform concentrations in healthy individuals. It also aimed to examine the concept of non-osmotic sodium storage in the skin following the HS diet by measuring body fluid status and systemic hemodynamic responses, as well as serum vascular endothelial growth factor C (VEGF-C) concentration. Forty-six young, healthy individuals completed a 7-day low-salt diet, followed by a 7-day HS diet protocol. The 7-day HS diet resulted in impaired NO-mediated endothelial vasodilation in peripheral microcirculation and conduit arteries, in increased eNOS, decreased nNOS, and unchanged iNOS concentration and NO serum level. The HS diet did not change the volume of interstitial fluid, the systemic vascular resistance or the VEGF-C serum level. These results indicate that the 7-day HS-diet induces systemic impairment of NO-mediated endothelial vasodilation, while dissociation in the eNOS and nNOS response indicates complex adaptation of main NO-generating enzyme isoforms to HS intake in healthy individuals. Our results failed to support the concept of non-osmotic sodium storage.

Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure: A Randomized, Placebo-Controlled, Double-Blind Study

Evidence for modulating the sodium chloride (NaCl) intake of patients hospitalized with acute heart failure (AHF) is inconclusive. Salt restriction may not benefit; hypertonic saline may aid diuresis. To compare the safety and efficacy of oral NaCl during intravenous (IV) diuretic therapy in renal function and weight. Seventy hospitalized patients with AHF who were being treated with IV furosemide infusion consented to receive, randomly, 2 grams of oral NaCl or placebo 3 times a day in a double-blind manner during diuresis. Treatment efficacy (bivariate primary endpoints of change in serum creatinine levels and change in weight) was measured at 96 hours, and adverse safety events were tracked for 90 days. Sixty-five patients (34 NaCl, 31 placebo) were included for analysis after 5 withdrew. A median of 13 grams of NaCl was given compared to placebo. At 96 hours, there was no significant difference between treatment groups with respect to the primary endpoint (P = 0.33); however, the trial was underpowered, and there was greater than expected standard deviation in weight change. The mean change in creatinine levels and weight was 0.15 ± 0.44 mg/dL and 4.6 ± 4.2 kg in the placebo group compared with 0.04 ± 0.40 mg/dL and 4.0 ± 4.3 kg in the NaCl group (P = 0.30 and 0.57, respectively). Across efficacy and safety endpoints, we observed no significant difference between the 2 groups other than changes in serum sodium levels (-2.6 ± 2.7 in the placebo group and -0.3 ± 3.3 mEq/L in the NaCl group; P < 0.001) and in serum blood urea nitrogen levels (11 ± 15 in the placebo group; 3.1 ± 13 mEq/L in the NaCl group; P = 0.025). In this single-center study, liberal vs restrictive oral sodium chloride intake strategies did not impact the safety and efficacy of intravenous diuretic therapy in patients with AHF. (ClinicalTrials.gov registration NCT04334668.).

Association Of Social Support With Symptom Status Among Patients With Heart Failure: The Mediating Effects Of Attitude, Subjective Norm, And Perceived Behavioral Control Toward Following A Low-sodium Diet

Association Of Social Support With Symptom Status Among Patients With Heart Failure: The Mediating Effects Of Attitude, Subjective Norm, And Perceived Behavioral Control Toward Following A Low-sodium Diet

Symptom: Vertigo After Labyrinthectomy

Symptom: Vertigo After Labyrinthectomy

Impact of orthotopic liver transplantation on serum lipid level and growing development in patients with homozygous or compound heterozygous familial hypercholesterolemia

Objective: To investigate the impact of orthotopic liver transplantation on serum lipid and growing development in patients with homozygous (HoFH) or compound heterozygotes (cHeFH) familial hypercholesterolemia. Methods: Patients who were treated in Peking Union Medical College Hospital from August 2019 to August 2021, entered the rare disease database and underwent liver transplantation, were included in this single center retrospective cohort study. The height for age Z score (HAZ) and length for age Z score (WAZ) at birth, at the time of transplantation and one year after transplantation were calculated respectively by collecting demographic characteristics, clinical manifestations, echocardiography, lipid-lowering treatment, blood lipid level data and donor characteristics data of liver transplantation. The serum cholesterol level and growing development changes before and after liver transplantation were evaluated. Results: A total of five patients with HoFH or cHeFH, including two females, were included in this study. The median age was 10 years (6-22 years). The median follow up duration was 28 months (24-33 months). All HoFH or cHeFH patients in this study received the maximum daily dosage of the lipid-lowering drug combined with low salt and low-fat diet control treatment for at least 3 months before orthotopic liver transplantation. The average level of total cholesterol (TC) decreased by 27% compared with that before treatment, the level of low-density lipoprotein cholesterol (LDL-C) decreased by 21% after 3 months treatment. There was no intervention of lipid-lowering therapy after operation. One month after liver transplantation, the average levels of TC and LDL-C further decreased rapidly by 68% and 76% respectively. One year after liver transplantation, the level of LDL-C decreased from (17.1±1.6)mmol/L without any intervention before transplantation to (3.0±0.7)mmol/L, and remained stable thereafter. In addition, compared with no intervention before liver transplantation, the serum triglyceride (TG) level decreased after the maximum daily dosage of the lipid-lowering drug and low salt and low-fat diet control for 3 months ((1.88±0.27) mmol/L vs. (1.12±0.55)mmol/L, P=0.031), and the HDL-C level also decreased significantly ((1.95±0.49)mmol/L vs. (0.95±0.30)mmol/L, P=0.006) at the same time period. TG and HDL-C remained stable after liver transplantation during the 24-month follow-up period (P>0.05). One and two years after liver transplantation, there was no significant difference in height and weight, malnutrition and growth retardation between the patients in this cohort and Chinese children of the same age. Conclusion: Early liver transplantation is a feasible and effective treatment option for HoFH or cHeFH patients with extremely high serum low-density lipoprotein cholesterol levels.

Post-salt magmatism in the Campos Basin, offshore SE Brazil: style, distribution, and relationship to salt tectonics

Substantial magmatism occurred during the development of the marginal basins of the central and southern South Atlantic. Situated on the Brazilian side of the central segment, the Campos and Santos basin represent a transitional margin, located between the magma-rich margin in the north and the magma-poor margin in the south. In addition to magmatism associated with the initiation of continental rifting, the southeast Brazilian basins experienced three main magmatic events; one during the early post-rift (i.e., sag stage) and two during the late post-rift (i.e., passive margin stage), both occurring after deposition of a thick, late Aptian salt layer. The products of post-salt, intrusive and extrusive magmatism in the southern Campos Basin are imaged in seismic reflection data and have been directly penetrated by boreholes, yet they remain poorly understood in terms of their style, detailed geometry, and distribution. Furthermore, the temporal, spatial and possibly genetic relationships between these post-salt igneous products and salt-tectonics are largely unknown. Documenting these possible salt-magma interactions is important to understanding the tectono-stratigraphic evolution of Campos Basin and other salt-bearing passive margin basins subject to magmatic activity. We use 2D and 3D seismic reflection and borehole data from the southeastern Campos Basin, offshore Brazil to map and characterize post-salt igneous sills and volcanoes, and to understand the interaction between salt tectonics and igneous products. We identified 99 sills emplaced within uppermost Aptian-to-Maastrichtian strata, 83 emplaced above the salt and 16 intra-salt, and 15 volcanoes within Upper Cretaceous-to-lower Paleogene strata, associated with a >310 km2 lava field. We also identify four, subsalt-sourced, vent-like structures, which vary in age from Paleogene to Late Cretaceous. Salt and overburden structures define a domain of extensional deformation on a base-salt basement high, and a domain of contractional deformation in the adjacent basement low. The relationship between igneous intrusions and salt tectonics is complex, i.e., in areas where they are common, sills appear to have locally restricted salt flow and the growth of large salt structures, whereas in other cases, salt structures and overlying faults appear to have partially acted as pathways to intruding magma, allowing it to ascend to relatively shallow depths. Extrusive igneous products exclusively developed after the main phase of salt movement. However, salt distribution influenced the location of volcanoes, given the latter developed where salt is welded or very thin. Salt flow and thickness also controlled the distribution of lava flow products, which accumulated in structural lows between large salt tectonic structures. Our work indicates a complex relationship between salt tectonics and magmatic emplacement that impact the post-rift evolution of Campos Basin.

Moderate dietary salt restriction improves blood pressure and mental well-being in patients with primary aldosteronism: The salt CONNtrol trial.

Primary aldosteronism (PA) is a frequent cause of hypertension. Aldosterone excess together with high dietary salt intake aggravates cardiovascular damage, despite guideline-recommended mineralocorticoid receptor antagonist (MRA) treatment. To investigate the antihypertensive impact of a moderate dietary salt restriction and associated physiological changes, including mental well-being. A total of 41 patients with PA on a stable antihypertensive regimen-including MRA-followed a dietary salt restriction for 12 weeks with structured nutritional training and consolidation by a mobile health app. Salt intake and adherence were monitored every 4 weeks using 24-h urinary sodium excretion and nutrition protocols. Body composition was assessed by bioimpedance analysis and mental well-being by validated questionnaires. Dietary salt intake significantly decreased from 9.1 to 5.2g/d at the end of the study. In parallel, systolic (130 vs. 121mmHg) and diastolic blood pressure (BP) (84 vs. 81mmHg) improved significantly. Patients' aptitude of estimating dietary salt content was refined significantly (underestimation by 2.4 vs. 1.4g/d). Salt restriction entailed a significant weight loss of 1.4kg, improvement in pulse pressure (46 vs. 40mmHg) and normalization of depressive symptoms (PHQD scale, p<0.05). Salt restriction, cortisol after dexamethasone suppression test and dosage of renin-angiotensin-aldosterone-system (RAAS) blockers were independently associated with BP reduction. A moderate restriction of dietary salt intake in patients with PA substantially reduces BP and depressive symptoms. Moreover, the findings underline that a sufficient RAAS blockade seems to augment the effects of salt restriction on BP and cardiovascular risk.

Molecular and Epigenetic Control of Aldosterone Synthase, CYP11B2 and 11-Hydroxylase, CYP11B1.

Aldosterone and cortisol serve important roles in the pathogenesis of cardiovascular diseases and metabolic disorders. Epigenetics is a mechanism to control enzyme expression by genes without changing the gene sequence. Steroid hormone synthase gene expression is regulated by transcription factors specific to each gene, and methylation has been reported to be involved in steroid hormone production and disease. Angiotensin II or potassium regulates the aldosterone synthase gene, CYP11B2. The adrenocorticotropic hormone controls the 11b-hydroxylase, CYP11B1. DNA methylation negatively controls the CYP11B2 and CYP11B1 expression and dynamically changes the expression responsive to continuous stimulation of the promoter gene. Hypomethylation status of the CYP11B2 promoter region is seen in aldosterone-producing adenomas. Methylation of recognition sites of transcription factors, including cyclic AMP responsive element binding protein 1 or nerve growth factor-induced clone B, diminish their DNA-binding activity. A methyl-CpG-binding protein 2 cooperates directly with the methylated CpG dinucleotides of CYP11B2. A low-salt diet, treatment with angiotensin II, and potassium increase the CYP11B2 mRNA levels and induce DNA hypomethylation in the adrenal gland. A close association between a low DNA methylation ratio and an increased CYP11B1 expression is seen in Cushing's adenoma and aldosterone-producing adenoma with autonomous cortisol secretion. Epigenetic control of CYP11B2 or CYP11B1 plays an important role in autonomic aldosterone or cortisol synthesis.

Aortic Stiffness: A Major Risk Factor for Multimorbidity in the Elderly.

Multimorbidity, the coexistence of multiple health conditions in an individual, has emerged as one of the greatest challenges facing health services, and this crisis is partly driven by the aging population. Aging is associated with increased aortic stiffness (AoStiff), which in turn is linked with several morbidities frequently affecting and having disastrous consequences for the elderly. These include hypertension, ischemic heart disease, heart failure, atrial fibrillation, chronic kidney disease, anemia, ischemic stroke, and dementia. Two or more of these disorders (multimorbidity) often coexist in the same elderly patient and the specific multimorbidity pattern depends on several factors including sex, ethnicity, common morbidity routes, morbidity interactions, and genomics. Regular exercise, salt restriction, statins in patients at high atherosclerotic risk, and stringent blood pressure control are interventions that delay progression of AoStiff and most likely decrease multimorbidity in the elderly.

Aldosterone Synthase Inhibitors and Dietary Interventions: A Combined Novel Approach for Prevention and Treatment of Cardiovascular Disease.

Systemic hypertension (HTN) is the hallmark of cardiovascular disease and the forerunner of heart failure. These associations have been established over decades of research on essential HTN. Advancements in the treatment of patients diagnosed with HTN, consisting of alpha- or beta-adrenergic receptor blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide, or aldosterone receptor blockers known as anti-mineralocorticoids, in the presence or absence of low sodium salt diets, often fail to control blood pressure adequately to prevent morbidity and mortality. Low sodium diets have had limited success in controlling HTN because low sodium intake is associated with renin-angiotensin-aldosterone system upregulation. Therefore, upregulating aldosterone secretion, sodium, and water retention which, in turn, moves the blood pressure back toward the range of HTN dictated by the baroreceptor reset value, as a compensatory mechanism, especially in resistant HTN. These impediments to blood pressure control in HTN may have been effectively circumvented by the advent of a new class of drugs known as aldosterone synthase inhibitors, represented by baxdrostat.The mechanism of action of baxdrostat as an aldosterone synthase inhibitor demonstrates the inextricable linkage between sodium and blood pressure regulation. Theoretically, combining a low sodium diet with the activity of this aldosterone synthesis inhibitor should alleviate the adverse effect of renin-angiotensin-aldosterone system upregulation. Aldosterone synthesis inhibition should also decrease the oxidative stress and endothelial dysfunction associated with HTN, causing more endothelial nitric oxide synthesis, release, and vasorelaxation. To the best of our knowledge, this is the first systematic review to summarize evidence-based articles relevant to the use of a novel drug (aldosterone synthase inhibitor) in the treatment of HTN and cardiovascular disease. Making the current database of relevant information on baxdrostat and other aldosterone synthase inhibitors readily available will, no doubt, aid physicians and other medical practitioners in their decision-making about employing aldosterone synthase inhibitors in the treatment of patients.

Sodium restriction and insulin resistance: A review of 23 clinical trials

Background: Many clinicians recommend low-salt diets for lowering blood pressure but there may be unintended consequences such as worsening insulin resistance.Aim: This paper aimed to find human clinical studies looking at low-salt diets on markers of glucose and insulin.Methods: We reviewed PubMed using the search terms ‘sodium’, ‘insulin’ and ‘insulin resistance’ and found 23 human clinical studies testing low-salt diets showing negative harms on insulin or glucose.Results: Twenty-three human clinical trials have shown that low-salt diets lead to systemic or vascular insulin resistance, glucose intolerance, elevated fasting insulin and/or elevations in glucose and/or insulin levels after an oral glucose tolerance test.Conclusion: We discovered 23 human clinical studies showing that low-salt diets worsen markers of insulin and glucose. Caution is advised when recommending salt restriction for blood pressure control as this may lead to worsening insulin resistance.Contribution: This review has revealed that low salt diets can induce insulin resistance.

A low-salt diet with candesartan administration is associated with acute kidney injury in nephritis by increasing nitric oxide

A low-salt diet may activate the renin-angiotensin-aldosterone system (RAAS) and is often applied simultaneously with RAAS inhibitors, especially for treatment of proteinuric nephritis. To explore the effect of a low-salt diet combined with angiotensin receptor blockers (ARB) on kidney function, the proteinuric nephritis model was induced by single intravenous injection of doxorubicin, and then the SD rats were administrated with candesartan intraperitoneal injection and fed with different salt diets. Rats with low-salt plus candesartan, not either alone, experienced acute kidney injury (AKI) at day 7 and could not self-restore when extending the experiment time from 7 days to 21 days, unless switching low-salt to normal-salt. Among three nitric oxide synthetases (NOS), endothelial NOS (eNOS) was obviously elevated and PI3K-Akt-eNOS signal pathway was activated. NG-Nitro-L-Arginine Methyl Ester (L-NAME), an eNOS inhibitor, reversed the decreased blood pressure and recovered the kidney dysfunction induced by low-salt with candesartan. The increased TUNEL-positive cells, Bax/Bcl-2 and cleaved-caspase3 protein abundance was ameliorated by L-NAME in vivo. In vitro, sodium nitroprusside, a nitric oxide donor, can also increase Bax/Bcl-2 and cleaved-caspase3 protein level in HK-2 cell. Thus, low-salt diet combined with candesartan in nephritis rats led to AKI, and the mechanism involved the increase of eNOS/NO, which linked to the decrease of blood pressure and the increase of apoptosis. This study provides practical guidance for salt intake in cases of RAS inhibitor usage clinically.

Home blood pressure-lowering effect of digital therapeutics in hypertension: impact of body weight and salt intake.

Lifestyle modifications, including body weight reduction and salt restriction, help reduce blood pressure (BP). This study investigated the effects of body mass index (BMI) and salt intake on home BP reductions in unmedicated patients with hypertension receiving guideline-based lifestyle modification from doctors (control group) or with the addition of a digital therapeutics intervention. Data from the HERB Digital Hypertension 1 (HERB-DH1) pivotal trial were analyzed. Home BP was measured for 7 days before each study visit (baseline, and 4/8/12 weeks). Body weight was measured at each visit and salt intake questionnaire was answered at baseline and 12 weeks. This analysis included 302 patients with sufficient home BP monitoring data (digital therapeutics: 156; control group: 146). The reduction in morning home SBP from baseline to 12 weeks was significantly greater in the digital therapeutics vs. control group for patients with baseline BMI ≥ 25 kg/m2 and higher salt intake group (self-reported salt intake score ≥ 14) (-5.1 mmHg, p < 0.01). Patients in the digital therapeutics group who experienced a reduction in BMI and an improvement in salt intake score during the 12-week study also had a significantly greater reduction in morning home SBP compared with patients in the control group (-7.2 mmHg, p < 0.01). The digital therapeutic intervention reduced home BP the most in unmedicated patients with hypertension with high baseline BMI and salt intake score. Those with improvements in both BMI and salt intake during the digital therapeutics intervention achieved the greatest reduction in home BP vs. control.Clinical trial registration: Japan Registry of Clinical Trials (jRCT2032190148).

Inverse salt sensitivity in normotensive adults: role of demographic factors.

Salt sensitivity and inverse salt sensitivity [ISS; a reduction in blood pressure (BP) on a high sodium diet] are each associated with increased incidence of hypertension. The purpose of this analysis was to determine the prevalence of ISS in normotensive adults and whether ISS is associated with any demographic characteristic(s). Healthy normotensive, nonobese adults [ n = 84; 43 women; age = 37 ± 13 years; baseline mean arterial pressure (MAP) = 89 ± 8 mmHg] participated in a controlled feeding study, consuming 7-day low-sodium (20 mmol sodium/day) and high-sodium (300 mmol sodium/day) diets. Twenty-four-hour ambulatory BP was assessed on the last day of each diet. ISS was defined as a reduction in 24-h MAP more than 5 mmHg, salt sensitivity as an increase in MAP more than 5 mmHg and salt resistance as a change in MAP between -5 and 5 mmHg from low sodium to high sodium. Using this cutoff, 10.7% were ISS, 76.2% salt resistant, and 13.1% salt sensitive. Prevalence of ISS was similar between sexes and age groups ( P > 0.05). However, ISS was more prevalent in those with normal BMI (15.8% ISS) compared with those with overweight BMI (0% ISS; P < 0.01). Interestingly, classification of participants using a salt sensitivity index (ΔMAP/Δ urinary sodium excretion) categorized 21.4% as ISS, 48.8% salt resistant, and 29.8% salt sensitive. Overall, we found that the prevalence of ISS was 10.7% (5 mmHg cutoff) or 21.4% (salt sensitivity index), and that ISS was associated with lower BMI. These results highlight the importance of future work to understand the mechanisms of ISS and to standardize salt sensitivity assessment.

Hypertension in Primary Aldosteronism Is Initiated by Salt-Induced Increases in Vascular Resistance With Reductions in Cardiac Output.

Few studies have investigated the hemodynamic mechanism whereby primary aldosteronism causes hypertension. The traditional view holds that hyperaldosteronism initiates hypertension by amplifying salt-dependent increases in cardiac output (CO) by promoting increases in sodium retention and blood volume. Systemic vascular resistance (SVR) is said to increase only as a secondary consequence of the increased CO and blood pressure. However, mounting evidence indicates that aldosterone can influence multiple pathways regulating vascular tone. We investigated the primary hemodynamic mechanism whereby hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension. In unilaterally nephrectomized male Sprague-Dawley rats given infusions of aldosterone or vehicle, we used chronically implanted arterial pressure probes and Doppler ultrasonic flow probes to continuously monitor changes in mean arterial pressure, CO, and SVR 24 hours/day, 7 days/week in response to increases in salt intake. In vehicle-treated control rats, switching from a low-salt diet to a high-salt diet initiated modest increases in mean arterial pressure by increasing SVR while simultaneously decreasing heart rate and CO. In aldosterone-treated rats compared with control rats, switching from a low-salt diet to a high-salt diet initiated significantly greater increases in mean arterial pressure and SVR and significantly greater decreases in heart rate and CO. Aldosterone promoted salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in SVR while decreasing CO. Increases in CO are not required for the initiation or maintenance of hypertension. These findings challenge the traditional view of the hemodynamic mechanisms that cause hypertension in primary aldosteronism.

Ultrastructure of Adrenal Glands in Sodium-deficient Pregnant Rats

The ultrastructure of the zona glomerulosa of the rat adrenal was studied in nonpregnant and pregnant animals receiving either adequate or restricted sodium intakes. Data on weight gain and food intake, hematocrit value and plasma sodium and potassium concentrations, histological observations, and the reproductive performance of pregnant animals were used in interpreting ultrastructural findings. Striking ultrastructural characteristics distinguished cells from the sodium-restricted pregnant animals from those of the other ex perimental groups. In particular, there were numerous lysosomes, autophagic vacuoles and cytoplasmic vacuoles devoid of cellular material. These pathologi cal cellular changes should be considered in evaluating the practice of prescrib ing sodium-restricted diets during normal human pregnancy. J. Nutr. 101: 1045-1056, 1971.