Dietary Salt Loading Research Articles

GENETIC VARIANCE IN HEPARAN SULFATION IS ASSOCIATED WITH SALT-SENSITIVITY: A GENE-ENVIRONMENT ANALYSIS

Objective: The high heritability of salt sensitivity suggests an essential role for genetic variants in the relationship between sodium intake and blood pressure (BP). Candidate gene studies have mainly focused on renal and vascular pathways, but the role of glycosaminoglycan (GAG) genes, which are crucial for salinity tolerance, remains to be elucidated. Design and method: Interactions between 54,126 variants in 130 GAG genes and daily sodium excretion on BP were explored in 20,420 EPIC-Norfolk subjects. UK Biobank (n=414,132) and the multi-ethnic HELIUS study (n=2,239) were used for validation. In HELIUS sodium intake was estimated with Food Frequency Questionnaires (FFQ). Urinary GAG composition in 57 Dutch origin HELIUS participants stratified by genotype were analyzed to assess the association between SNP and GAG difference. Also, urinary GAG composition in 12 healthy volunteers after a sodium intervention (7-day low (50 mmol Na+/day) and 7-day high (200 mmol Na+/day) diet) were studied to assess if differences in genotype are associated with different GAG expression. Results: The intron variant rs2892799, mapped to NDST3, showed the strongest interaction with sodium on mean arterial pressure (MAP) (FDR 0.03), and the intron variant rs9654628 mapped to HS3ST5 with sodium on systolic BP (FDR 0.03). These interactions were multi-ethnically validated (Fig 1A, B). When stratified for rs2892799 genotype, T-allele carriers had a significantly higher urinary expression of N-sulfated heparan sulfate epitope D0S0 (Fig1C). Conversely, upon dietary salt loading, urinary D0S0 expression differed substantially between salt-sensitive and salt-resistant individuals (Fig1D). Sodium-induced effects on this epitope were opposite in salt-sensitive in salt-resistant individuals. Conclusions: Genetic variants associated with NDST3 and HS3ST5 interact with relation between sodium consumption and BP. rs2892799 (NDST3) genotype results in a different expression of the N-sulfated D0S0 epitope. In turn, D0S0 expression is associated with salt-mediated BP increase, indicating that genetic GAG variation and metabolic GAG adaptation to a high salt environment might be important for human BP regulation.

Regulation of human salt-sensitivite hypertension by myeloid cell renin-angiotensin-aldosterone system.

Introduction: Salt sensitivity of blood pressure is a phenomenon in which blood pressure changes according to dietary sodium intake. Our previous studies found that high salt activates antigen presenting cells, resulting in the development of hypertension. The mechanisms by which salt-induced immune cell activation is regulated in salt sensitivity of blood pressure are unknown. In the current study, we investigated dietary salt-induced effects on the renin-angiotensin-aldosterone system (RAAS) gene expression in myeloid immune cells and their impact on salt sensitive hypertension in humans. Methods: We performed both bulk and single-cell sequencing analysis on immune cells with in vitro and in vivo high dietary salt treatment in humans using a rigorous salt-loading/depletion protocol to phenotype salt-sensitivity of blood pressure. We also measured plasma renin and aldosterone using radioimmunoassay. Results: We found that while in vitro high sodium exposure downregulated the expression of renin, renin binding protein and renin receptor, there were no significant changes in the genes of the renin-angiotensin system in response to dietary salt loading and depletion in vivo. Plasma renin in salt sensitive individuals tended to be lower with a blunted response to the salt loading/depletion challenge as previously reported. Discussion: These findings suggest that unlike systemic RAAS, acute changes in dietary salt intake do not regulate RAAS expression in myeloid immune cells.

Longitudinal changes in blood pressure are preceded by changes in albuminuria and accelerated by increasing dietary sodium intake

BackgroundDietary sodium is a well-known risk factor for cardiovascular and renal disease; however, direct evidence of the longitudinal changes that occur with aging, and the influence of dietary sodium on the age-associated alterations are scarce. MethodsC57BL/6 mice were maintained for 13 months on a low (LS, 0.02 % Na+), normal (NS, 0.3 % Na+) or high (HS, 1.6 % Na+) salt diet. We assessed 1) the longitudinal trajectories for two markers of cardiovascular and renal dysfunction (blood pressure (BP) and albuminuria), as well as hormonal changes, and 2) end-of-study cardiac and renal parameters. ResultsThe effect of aging on BP and kidney damage did not reach significance levels in the LS group; however, relative to baseline, there were significant increases in these parameters for animals maintained on NS and HS diets, starting as early as month 7 and month 5, respectively. Furthermore, changes in albuminuria preceded the changes in BP relative to baseline, irrespective of the diet. Circulating aldosterone and plasma renin activity displayed the expected decreasing trends with age and dietary sodium loading. As compared to LS – higher dietary sodium consumption associated with increasing trends in left ventricular mass and volume indices, consistent with an eccentric dilated phenotype. Functional and molecular markers of kidney dysfunction displayed similar trends with increasing long-term sodium levels: higher renovascular resistance, increased glomerular volumes, as well as higher levels of renal angiotensin II type 1 and mineralocorticoid receptors, and lower renal Klotho levels. ConclusionOur study provides a timeline for the development of cardiorenal dysfunction with aging, and documents that increasing dietary salt accelerates the age-induced phenotypes. In addition, we propose albuminuria as a prognostic biomarker for the future development of hypertension. Last, we identified functional and molecular markers of renal dysfunction that associate with long-term dietary salt loading,

Predisposition to cortical neurodegenerative changes in brains of hypertension prone rats

BackgroundSubstantial evidence suggests that hypertension is a significant risk factor for cognitive decline. However, it is unclear whether the genetic predisposition to hypertension is also associated with cellular dysfunction that promotes neurodegeneration.MethodsChanges in blood pressure were evaluated following dietary salt-loading or administration of a regular diet in Sabra Normotensive (SBN/y) and Sabra Hypertension-prone rats (SBH/y). We performed quantitative RT-PCR and immunofluorescence staining in brain cortical tissues before salt loading and 6 and 9 months after salt loading. To examine the expression of brain cortical proteins involved in the gene regulation (Histone Deacetylase-HDAC2; Histone Acetyltransferase 1-HAT1), stress response (Activating Transcription Factor 4-ATF4; Eukaryotic Initiation Factor 2- eIF2α), autophagy (Autophagy related 4A cysteine peptidase- Atg4a; light-chain 3-LC3A/B; mammalian target of rapamycin complex 1- mTORC1) and apoptosis (caspase-3).ResultsPrior to salt loading, SBH/y compared to SBN/y expressed a significantly higher level of cortical HAT1 (protein), Caspase-3 (mRNA/protein), LC3A, and ATF4 (mRNA), lower levels of ATG4A (mRNA/protein), LC3A/B, HDAC2 (protein), as well as a lower density of cortical neurons. Following dietary salt loading, SBH/y but not SBN/y developed high blood pressure. In hypertensive SBH/y, there was significant upregulation of cortical HAT1 (protein), Caspase-3 (protein), and eIF2α ~ P (protein) and downregulation of HDAC2 (protein) and mTORC1 (mRNA), and cortical neuronal loss.ConclusionsThe present findings suggest that genetic predisposition to hypertension is associated in the brain cortex with disruption in autophagy, gene regulation, an abnormal response to cellular stress, and a high level of cortical apoptosis, and could therefore exacerbate cellular dysfunction and thereby promote neurodegeneration.

PS-BPB10-3: MOLECULAR INSIGHT INTO SALT-SENSITIVITY; THE ROLE OF ATF3 AND THE GENERATION OF TUBULAR SPECIFIC KO MICE. (2)

Objective: Atf3 is transcriptionally activated according to intracellular Na concentrations. We found about 1.6 fold to 2.5 fold gene expression enhancements in kidney of Nedd4 2 C2 KO mice due to oral salt intakes and diuretics treatments. Aim of this study is to elucidate significance of Atf3 gene for salt-sensitivity by dietary salt loading and furosemide treatment for tubular specific Atf3 KO mice examining blood pressure, body weight, urine volume, water intake with genetic analyses. Methods: We performed metabolic cage experiments for male Ksp-cre (minus) Atf3 flox/flox mice (N = 5) and male Ksp-cre (+) Atf3 flox/flox mice (N = 10) with 7–8 wks old for subsequent protocol. After 1 week habituation period, experiments were done for 3 days normal salt intake, 5 days high salt intake, and 5 days high salt intake with furosemide treatment (40 mg/kg, ip), respectively. We measured blood pressure by tail cuff methods at day 0, day 8, and day 12. During experimental periods, body weight, water intake and urine volumes are measured daily. Results: We could not find significant differences among body weight, water intake and urine volume between two groups. After high oral salt intake and intra-peritoneal furosemide injection, we found blood pressure of cre (+) Atf3 flox/flox mice were significantly higher than cre (minus) Atf 3 flox/flox mice. (p < 0.001, 119.6 ± 1.4 mmHg vs 112.8 mmHg) Additionally, we found significant expression change of both classic renin and alternative renin in tubules between two groups by quantitative RT PCR and immunohisto chemistry imaging for kidney. Conclusions: Tubular-specific Atf3 KO mice have elevated blood pressure sensitive to salt and furosemide treatment. Because furosemide treatment might induce enhancement of intra-cellular Na ion concentration, Atf3 gene is responsible for adaptations for intra-cellular Na concentration change through tubular renin expressions.

Dietary salt supplementation adversely affects thermal acclimation responses of flight ability in Drosophila melanogaster

Cold acclimation may enhance low temperature flight ability, and salt loading can alter an insects’ cold tolerance by affecting their ability to maintain ion balance in the cold. Presently however, it remains unclear if dietary salt impacts thermal acclimation of flight ability in insects. Here, we examined the effect of a combination of dietary salt loading (either NaCl or KCl) and low temperature exposure on the flight ability of Drosophila melanogaster at low (15 °C) and benign (optimal, 22 °C) temperatures. Additionally, we determined whether dietary salt supplementation translates into increased K+ and Na+ levels in the bodies of D. melanogaster. Lastly, we determined whether salt supplementation impacts body mass and wing morphology, to ascertain whether any changes in flight ability were potentially driven by flight-related morphometric variation. In control flies, we find that cold acclimation enhances low temperature flight ability over non-acclimated flies confirming the beneficial acclimation hypothesis. By contrast, flies supplemented with KCl that were cold acclimated and tested at a cold temperature had the lowest flight ability, suggesting that excess dietary KCl during development negates the beneficial cold acclimation process that would have otherwise taken place. Overall, the NaCl-supplemented flies and the control group had the greatest flight ability, whilst those fed a KCl-supplemented diet had the lowest. Dietary salt supplementation translated into increased Na+ and K+ concentration in the body tissues of flies, confirming that dietary shifts are reflected in changes in body composition and are not simply regulated out of the body by homeostasis over the course of development. Flies fed with a KCl-supplemented diet tended to be larger with larger wings, whilst those reared on the control or NaCl-supplemented diet were smaller with smaller wings. Additionally, the flies with greater flight ability tended to be smaller and have lower wing loading. In conclusion, dietary salts affected wing morphology as well as ion balance, and dietary KCl seemed to have a detrimental effect on cold acclimation responses of flight ability in D. melanogaster.

Impact of maternal intermittent fasting during pregnancy on cardiovascular, metabolic and renal function in adult rat offspring.

Pregnant Muslim women are exempt from fasting during Ramadan; however a majority are reported to fast. The impact of this form of maternal intermittent fasting (IF) on fetal development and offspring health is not well defined. Using a rat model, we have shown previously that maternal IF results in fetal growth restriction accompanied by changes in placental nutrient transport function. The aim of this study was to assess cardiovascular, metabolic and renal function in adult offspring of IF-exposed dams. Food was withheld from Wistar rats from 17:00 to 09:00 daily throughout pregnancy; controls had ad libitum access to food. Birth weight was unaffected; however male IF pups grew more slowly up to 10 weeks of age (P < 0.01) whereas IF females matched their control counterparts. Systolic blood pressure (SBP), glucose tolerance and basal renal function at 14 weeks were not affected by IF exposure. When offered saline solutions (0.9–2.1%) to drink, females showed a greater salt preference than males (P < 0.01); however there were no differences between dietary groups. A separate group of pups was weaned onto a 4% NaCl diet. SBP increased in IF pups sooner, at 7 weeks (P < 0.01), than controls which became hypertensive from 10 weeks. Renal function did not appear to differ; however markers of renal injury were elevated in IF males (P < 0.05). Maternal IF does not affect resting cardiovascular, metabolic and renal function; but when challenged by dietary salt load male IF offspring are more prone to renal injury.

High dietary salt intake increases urinary NGAL excretion and creatinine clearance in healthy young adults.

In rodents and older patients with elevated blood pressure (BP), high dietary sodium increases excretion of biomarkers of kidney injury, but it is unclear whether this effect occurs in healthy young adults. The purpose of this study was to determine whether short-term high dietary salt increases urinary excretion of the kidney injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in healthy young adults. Twenty participants participated in a double-blind, placebo-controlled, randomized crossover study. For 10 days each, participants were asked to consume salt (3,900 mg sodium) or placebo capsules. We measured BP during each visit, obtained 24-h urine samples for measurements of electrolytes, NGAL, and KIM-1, and assessed creatinine clearance. Compared with placebo, salt loading increased daily urinary sodium excretion (placebo: 130.3 ± 62.4 mmol/24 h vs. salt: 287.2 ± 72.0 mmol/24 h, P < 0.01). There was no difference in mean arterial BP (placebo: 77 ± 7 mmHg vs. salt: 77 ± 6 mmHg, P = 0.83) between conditions. However, salt loading increased the urinary NGAL excretion rate (placebo: 59.8 ± 44.4 ng/min vs. salt: 80.8 ± 49.5 ng/min, P < 0.01) and increased creatinine clearance (placebo: 110.5 ± 32.9 mL/min vs. salt: 145.0 ± 24.9 mL/min, P < 0.01). Urinary KIM-1 excretion was not different between conditions. In conclusion, in healthy young adults 10 days of dietary salt loading increased creatinine clearance and increased urinary excretion of the kidney injury biomarker marker NGAL but not KIM-1.NEW & NOTEWORTHY In healthy young adults, 10 days of dietary salt loading increased creatinine clearance and increased urinary excretion of the kidney injury biomarker marker neutrophil gelatinase-associated lipocalin despite no change in resting blood pressure.

Prevalence Rate of Proteinuria and Metabolic Acidosis Among Kidney Transplant Recipients in a Tertiary Teaching Hospital and Its Relationship to Dietary Intake

Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in influencing proteinuria and metabolic acidosis remained uncertain. This study aims to determine the prevalence rate of proteinuria and metabolic acidosis among kidney transplant recipients (KTRs) and to study their relationship with dietary intake. We performed a cross-sectional study on KTRs with functioning renal allograft and at least 3 months post transplant. Dietary protein, salt, and dietary acid load were estimated using 24-hour urine collection. Demographic characteristics, concomitant medications, medical history, and laboratory results were obtained from electronic medical records. A total of 204 KTRs were recruited with median age of 48 years (interquartile range [IQR], 18 years); male to female ratio was 61:39. A total of 79.9% (n=163) were living related kidney transplants. The median duration after transplant was 71 months (IQR, 131 months), and median eGFR was 65 mL/min/1.73 m2 (IQR, 25 mL/min/1.73 m2). The prevalence rates of proteinuria (defined as ≥ 0.5 g/d) and metabolic acidosis (defined as at least 2 readings of serum bicarbonate ≤ 22 mmol/L in the past 6 months) were 17.7 % and 6.2%, respectively. High dietary protein of > 1.2 g/kg ideal body weight (adjusted odds ratio, 3.13; 95% CI, 1.35-7.28; P=.008) was significantly associated with proteinuria. Dietary protein, salt, and acid load did not correlate with chronic metabolic acidosis. The prevalence rate of proteinuria is consistent with published literature, but metabolic acidosis rate is extremely low in our cohort. High protein intake (> 1.2 g/kg ideal body weight) is a risk factor of proteinuria and may have negative impact on KTR outcome.

Skin Sodium and Blood Pressure Regulation.

Hypertension is a major public health concern due to its high prevalence and increased risk of cardiovascular disease and mortality. Complex traits resulting from both genetic and environmental factors affect the development of hypertension. Among environmental factors, a high salt diet is an important cause for hypertension. Humans show a heterogeneous blood pressure (BP) response to sodium intake. Although the precise mechanisms for the association between salt sensitivity and hypertension have not been fully elucidated, renal sodium handling has been considered to play a pivotal role. However, this conventional view has recently been challenged in that a third compartment, namely, skin may have a role in the regulation of sodium homeostasis. Skin is comprised of a significant portion of interstitium, which is a major extracellular fluid compartment, and its complex capillary network regulates body temperature and skin perfusion. Growing evidence indicates that local regulatory action of cutaneous blood flow as well as salt and water metabolism is associated with systemic BP control. Previous experimental studies have shown that dietary salt loading resulted in nonosmotic sodium accumulation via glycosaminoglycans and lymphatics embedded in the skin that were mediated by several endogenous factors and attenuated an increase in BP. Studies in humans have also suggested that the skin serves as a buffer system for sodium storage and that skin sodium contributes to salt sensitivity and hypertension. Thus, skin sodium storage provides the possibility of being an additional buffering system in response to salt loading and concomitant BP changes in humans.

High salt diet impairs dermal tissue remodeling in a mouse model of IMQ induced dermatitis.

Recent animal studies, as well as quantitative sodium MRI observations on humans demonstrated that remarkable amounts of sodium can be stored in the skin. It is also known that excess sodium in the tissues leads to inflammation in various organs, but its role in dermal pathophysiology has not been elucidated. Therefore, our aim was to study the effect of dietary salt loading on inflammatory process and related extracellular matrix (ECM) remodeling in the skin. To investigate the effect of high salt consumption on inflammation and ECM production in the skin mice were kept on normal (NSD) or high salt (HSD) diet and then dermatitis was induced with imiquimod (IMQ) treatment. The effect of high salt concentration on dermal fibroblasts (DF) and peripheral blood mononuclear cells (PBMC) was also investigated in vitro. The HSD resulted in increased sodium content in the skin of mice. Inflammatory cytokine Il17 expression was elevated in the skin of HSD mice. Expression of anti-inflammatory Il10 and Il13 decreased in the skin of HSD or HSD IMQ mice. The fibroblast marker Acta2 and ECM component Fn and Col1a1 decreased in HSD IMQ mice. Expression of ECM remodeling related Pdgfb and activation phosphorylated (p)-SMAD2/3 was lower in HSD IMQ mice. In PBMCs, production of IL10, IL13 and PDGFB was reduced due to high salt loading. In cultured DFs high salt concentration resulted in decreased cell motility and ECM production, as well. Our results demonstrate that high dietary salt intake is associated with increased dermal pro-inflammatory status. Interestingly, although inflammation induces the synthesis of ECM in most organs, the expression of ECM decreased in the inflamed skin of mice on high salt diet. Our data suggest that salt intake may alter the process of skin remodeling.

RECEPTOR INTERACTING MOLECULE ATRAP AS MODULATOR OF RENAL SODIUM HANDLING AND PATHOLOGICAL BLOOD PRESSURE RESPONSE

Objective: Pathological activation of renal angiotensin II (Ang II) type 1 receptor (AT1R) signaling exerts stimulates renal tubular Na+ transporters including epithelial Na+ channel to increase renal sodium reabsorption. Design and method: In the course of an investigational search for a means to functionally and selectively modulate AT1R signaling for that purpose, a molecule directly interacting with the carboxyl-terminal cytoplasmic domain of AT1R was identified by employing yeast two-hybrid screening of a mouse kidney cDNA library and named AT1R-associated protein (ATRAP). Results: We showed that ATRAP promotes constitutive AT1R internalization so as to inhibit pathological AT1R activation in response to certain stimuli. In the kidney, ATRAP is abundantly distributed in epithelial cells along the renal tubules. The results employing genetic engineered mice with modified ATRAP expression showed that ATRAP plays a key role in the regulation of renal sodium handling and the modulation of blood pressure in response to pathological stimuli such as chronic Ang II infusion dietary high salt loading and 5/6 nephrectomy. Conclusions: Accumulating findings concerning functional and pathological roles of the novel receptor-interacting molecule ATRAP suggest that ATRAP would be a target of interest for hypertension in the cardiovascular and renal continuum.

Differential Role of Renal Alpha 1 Adreno Receptors Subtypes in Renal Vasculature in Normotensive and Hypertensive Conditions Subjected to High Dietary Salt Load

Chronic high salt intake is well known to be linked to cause an increase in the blood pressure and one of the pathogenic effects of high salt on blood pressure is vascular functional impairment. The effect of sodium on vasculature involves an increase in the vascular resistance that could triggers a rise in the blood pressure. Sodium-induced increase in vascular resistance is primarily independent of any change in blood pressure; however, it could be an initiating factor for increase in the blood pressure. Salt induced increase in the vascular resistance involves alterations in several vasoregulatory mechanisms as evidenced in various vascular beds. A mechanism exhibiting a substantial effect on vascular function is the alpha (α1)-adrenergic system that significantly influences vascular resistance, thereby affecting peripheral vascular resistance and blood pressure. This review focused on the effects of increase dietary sodium intake on the α1-adrenergic system in renal vascular beds under normotensive and hypertensive conditions. Because the α1-adrenergic regulations of renal vascular function and renal hemodynamics affect blood pressure to a great extent, renal vascular assessment was performed. Study reports enhanced renal vascular sensitivity to α1-adrenergic agonist in high sodium normotensive and hypertensive condition, this could be due to functional alterations in the renal α1-adrenoreceptor density. This provide additional evidence on the underlying vascular pathology in salt-induced hypertension.

Salt sensitivity and hypertension.

Salt sensitivity refers to the physiological trait present in mammals, including humans, by which the blood pressure (BP) of some members of the population exhibits changes parallel to changes in salt intake. It is commoner in elderly, females, Afro-Americans, patients with chronic kidney disease (CKD) and insulin resistance. Increased salt intake promotes an expansion of extracellular fluid volume and increases cardiac output. Salt-sensitive individuals present an abnormal kidney reaction to salt intake; the kidneys retain most of the salt due to an abnormal over-reactivity of sympathetic nervous system and a blunted suppression of renin-angiotensin axis. Moreover, instead of peripheral vascular resistance falling, salt-sensitive subjects present increased vascular resistance due mainly to impaired nitric oxide synthesis in endothelium. Recent studies have shown that part of the dietary salt loading accumulates in skin. Hypertensive and patients with CKD seem to have more sodium in skin comparing to healthy ones. However, we still have not fully explained the link between skin sodium, BP and salt sensitivity. Finally, although salt sensitivity plays a meaningful role in BP pathophysiology, it cannot be used by the physician in everyday patient's care, mainly due to lack of a simple and practical diagnostic test.

Does Dietary Salt Loading Impair Ambulatory Blood Pressure Variability? As Yet an Unresolved Issue

Does Dietary Salt Loading Impair Ambulatory Blood Pressure Variability? As Yet an Unresolved Issue

Salt-sensitive blood pressure rise in type 1 diabetes patients is accompanied by disturbed skin macrophage influx and lymphatic dilation—a proof-of-concept study

Type 1 diabetes patients are more prone to have hypertension than healthy individuals, possibly mediated by increased blood pressure (BP) sensitivity to high salt intake. The classical concept proposes that the kidney is central in salt-mediated BP rises, by insufficient renal sodium excretion leading to extracellular fluid volume expansion. Recent animal-derived findings, however, propose a causal role for disturbance of macrophage-mediated lymphangiogenesis. Its relevance for humans, specifically type 1 diabetes patients, is unknown. The present study aimed to assess responses of type 1 diabetes patients to a dietary salt load with regard to BP, extracellular fluid volume (using precise iohexol measurements), and CD163+ macrophage and lymphatic capillary density in skin biopsies. Also, macrophage expression of HLA-DR (a proinflammatory marker) and CD206 (an anti-inflammatory marker) was assessed. Type 1 diabetes patients (n = 8) showed a salt-sensitive BP increase without extracellular fluid volume expansion. Whereas healthy controls (n = 12), who had no BP increase, showed increased skin CD163+ and HLA-DR+ macrophages and dilation of lymphatic skin vasculature after the dietary salt load, these changes were absent (and in case of HLA-DR more heterogenic) in type 1 diabetes patients. In conclusion, we show that salt sensitivity in type 1 diabetes patients cannot be explained by the classical concept of extracellular fluid volume expansion. Rather, we open up a potential role for macrophages and the lymphatic system. Future studies on hypertension and diabetes need to scrutinize these phenomena.

The immune system cell populations were increased in salt-induced hypertensive rats without an increase in the serum testosterone level (Short communication).

The consumption of dietary salt has significantly increased globally, especially in the developed countries. High dietary salt intake has been linked to onset and complications in hypertension with a dimorphism tendency. There is scanty information about the influence of high salt diet on the immune cell population and androgen level in circulation. Male Sprague-Dawley rats of 8weeks old were used for this study. They were divided into control (fed 0.1% salted feed) and salt-loaded groups (fed 8% salted feed) for 8 weeks. All experimental rats were allowed access to clean drinking water; daily feed consumption was measured in addition to weekly weight. On confirmation of hypertension using PowerLab® data acquisitions system, the rats were sacrificed and blood samples were collected into EDTA and sterile sample bottles. EDTA-blood samples were used for white blood cell and CD4 counts while the serum was used for hormonal assays. All salt-loaded rats became hypertensive, with a significant increase in total white blood cell, lymphocyte, neutrophil, monocyte, and CD4 cell counts. However, the eosinophil count was significantly decreased in salt-loaded rats. This study showed no change in the serum testosterone in salt-loaded male rats compared with control. In summary, dietary salt loading while precipitating hypertension also activated increased production of white blood cells and CD4 cells without any change in the serum testosterone level.

Novel Mechanism for Buffering Dietary Salt in Humans: Effects of Salt Loading on Skin Sodium, Vascular Endothelial Growth Factor C, and Blood Pressure.

High dietary sodium intake triggers increased blood pressure (BP). Animal studies show that dietary salt loading results in dermal Na+ accumulation and lymphangiogenesis mediated by VEGF-C (vascular endothelial growth factor C), both attenuating the rise in BP. Our objective was to determine whether these mechanisms function in humans. We assessed skin electrolytes, BP, and plasma VEGF-C in 48 healthy participants randomized to placebo (70 mmol sodium/d) and slow sodium (200 mmol/d) for 7 days. Skin Na+ and K+ concentrations were measured in mg/g of wet tissue and expressed as the ratio Na+:K+ to correct for variability in sample hydration. Skin Na+:K+ increased between placebo and slow sodium phases (2.91±0.08 versus 3.12±0.09; P=0.01). In post hoc analysis, there was a suggestion of a sex-specific effect, with a significant increase in skin Na+:K+ in men (2.59±0.09 versus 2.88±0.12; P=0.008) but not women (3.23±0.10 versus 3.36±0.12; P=0.31). Women showed a significant increase in 24-hour mean BP with salt loading (93±1 versus 91±1 mm Hg; P<0.001) while men did not (96±2 versus 96±2 mm Hg; P=0.91). Skin Na+:K+ correlated with BP, stroke volume, and peripheral vascular resistance in men but not in women. No change was noted in plasma VEGF-C. These findings suggest that the skin may buffer dietary Na+, reducing the hemodynamic consequences of increased salt, and this may be influenced by sex.

Chronic dietary salt stress mitigates hyperkalemia and facilitates chill coma recovery in Drosophila melanogaster

Chill susceptible insects like Drosophila lose the ability to regulate water and ion homeostasis at low temperatures. This loss of hemolymph ion and water balance drives a hyperkalemic state that depolarizes cells, causing cellular injury and death. The ability to maintain ion homeostasis at low temperatures and/or recover ion homeostasis upon rewarming is closely related to insect cold tolerance. We thus hypothesized that changes to organismal ion balance, which can be achieved in Drosophila through dietary salt loading, could alter whole animal cold tolerance phenotypes. We put Drosophila melanogaster in the presence of diets highly enriched in NaCl, KCl, xylitol (an osmotic control) or sucrose (a dietary supplement known to impact cold tolerance) for 24h and confirmed that they consumed the novel food. Independently of their osmotic effects, NaCl, KCl, and sucrose supplementation all improved the ability of flies to maintain K+ balance in the cold, which allowed for faster recovery from chill coma after 6h at 0°C. These supplements, however, also slightly increased the CTmin and had little impact on survival rates following chronic cold stress (24h at 0°C), suggesting that the effect of diet on cold tolerance depends on the measure of cold tolerance assessed. In contrast to prolonged salt stress, brief feeding (1.5h) on diets high in salt slowed coma recovery, suggesting that the long-term effects of NaCl and KCl on chilling tolerance result from phenotypic plasticity, induced in response to a salty diet, rather than simply the presence of the diet in the gut lumen.

Abstract 098: A Novel Mechanism for Buffering Dietary Salt in Humans: Effects of Salt Loading on Skin Sodium, VEGF-C and Blood Pressure

Introduction: Dietary sodium is an important trigger for hypertension. Animal studies show that the skin buffers dietary salt and salt-loading induces lymphangiogenesis mediated by VEGF-C, maintaining normal BP. Our primary objective was to determine whether increased skin Na + on salt loading attenuates the expected rise in blood pressure. Methods: We assessed skin and urine electrolytes, systemic haemodynamics, ambulatory BP and plasma VEGF-C in 48 healthy participants. Participants were placed on a low salt diet (70mmol sodium/day) and received placebo and slow sodium (200mmol daily for 7 days) in a randomised order. Skin Na + and K + concentrations were measured in mg/g tissue by inductively coupled plasma optical emission spectroscopy. Results were expressed as the ratio of Na + :K + to correct for variability in sample hydration. Plasma VEGF-C was analysed by ELISA. Results: Mean age was 30 ± 8 years (24 male). 24-hr urine Na + was higher following salt than placebo in males (221.9 ± 16.5 vs. 86.3 ± 10.3mmol, p &lt; 0.001) and females (227.1 ± 19.9 vs. 60.0 ± 6.8mmol, p &lt; 0.001). In males, skin Na + :K + was higher after salt loading (2.87 ± 0.12 vs. 2.59 ± 0.09 mg/g , p = 0.008), but not significantly different in females (3.36 ± 0.12 vs. 3.23 ± 0.10 mg/g, p = 0.49). Females showed a significant increase in 24-hr MAP with salt loading (88 ± 1 vs. 85 ± 1 mmHg, p=0.004) but not males (90 ± 2 vs. 90 ± 2 mm Hg, p = 0.91). In males only, skin Na + :K + correlated with supine MAP post-placebo (r = 0.52, p = 0.004) and post-salt (r = 0.51, p = 0.01). No significant change was noted in plasma VEGF-C. Conclusions: Salt loading causes an increase in BP in healthy females but not in males, whilst skin sodium rises in males. This indicates that the skin may buffer the haemodynamic consequences of increased salt intake in a gender-specific manner.