NaCl Intake Research Articles

Physical Activity and Urinary Sodium Excretion Circadian Rhythm: A Population-Based Cross-Sectional Pilot Study.

Background/Objectives: Blood pressure (BP) is characterized by a circadian rhythm (Circr) with lower nighttime values, called dipping. Non-dipping is associated with higher CVD risk. The Circr of urinary sodium excretion (NaCle), peaking during the day, is linked to BP patterns. Physical activity (PA) is known to improve BP control and enhance the dipping phenomenon, but its possible effect on NaCle remains unclarified. This study aimed to investigate the correlation between PA and the Circr of NaCle and to determine if the relationship is independent of age, sex, BP values, dipping pattern, and salt intake. Methods: A pilot cross-sectional analysis was conducted using data from the Ticino Epidemiological Stiffness Study, involving 953 participants in Switzerland. Data collection included standardized questionnaires, blood samples, 24 h urine collections, and ambulatory BP monitoring. Participants were categorized into sedentary, partially active, and active. The effect of PA, NaCl intake, and dipping on the day/night NaCle ratio was assessed with multivariable linear regressions. Results: Participants' median age was 49 years, with 78% having normal BP values and 47% exhibiting a dipping pattern; 51% were classified as sedentary and 22% as partially active. The median NaCl intake was 7.9 g/day. The youngest subjects had a higher hourly NaCle ratio compared to older subjects. Higher NaCl intake correlated with increased BP, a phenomenon more pronounced in men and younger subjects. The hourly day/night NaCle ratio positively correlates with dipping; however, PA did not show a significant correlation with the NaCle ratio. Conclusions: This study indicates that while the day/night NaCle ratio correlates with the dipping pattern, PA is unrelated to the circadian rhythm of renal sodium handling. The beneficial effects of PA on BP and cardiovascular health thus appear to be mediated through mechanisms other than NaCle. These are explorative findings only but relativize the need for further investigations on the topic.

Effects of sodium chloride intake on urea-N recycling and renal urea-N kinetics in lactating Holstein cows

The effects of high (2.5% of DM) versus normal dietary sodium chloride (NaCl) intake on renal urea-N kinetics and urea-N metabolism were investigated in 9 rumen-cannulated and multi-catheterized lactating dairy cows in a crossover design with 21-d periods. It was hypothesized that urinary urea-N excretion would be greater, and blood urea-N concentration lower in response to greater diuresis induced by high NaCl intake. Also, urea-N transport across ruminal and portal drained viscera (PDV) tissues was hypothesized to be affected by dietary sodium intake. A second experiment was conducted using 8 lactating cows in a crossover design with 14-d periods to test high NaCl (2.5% of DM) versus high KCl (3.2% of DM) intake on milk yield and milk urea-N concentrations. Experiment 1 showed that despite greater diuresis there was no effect of high NaCl intake on urinary urea-N excretion or blood urea-N concentration. The high NaCl intake did not affect rumen ammonia concentrations, total rumen VFA concentrations, ruminal venous - arterial concentration differences for ammonia, or ammonia absorption indicating that high NaCl did not adversely affect ruminal fermentation and microbial protein synthesis. High NaCl intake did not affect the total amount of urea-N transport from blood to gut, but ruminal venous - arterial concentration differences for urea-N were lower with high NaCl and ruminal extraction of arterial urea-N was numerically smaller, indicating that the ruminal epithelial urea-N transport was lower with high NaCl. Energy corrected milk yield was greater with high NaCl (3.2 ± 1.5 kg/d); however, milk urea-N concentrations were not affected by treatment. In experiment 2, ECM was greater with NaCl (1.4 ± 0.31 kg/d) compared with KCl (30.2 and 28.8 ± 0.91 kg ECM / d, respectively). Milk urea-N concentration was lower with KCl, suggesting a urea-N lowering effect in milk not evident with high NaCl intake. In conclusion, the present data show that dietary Na intake of 12-13 g/kg DM was followed by greater diuresis but did not impact urea-N excretion or blood urea-N concentration. High NaCl intake did not affect the total amount of urea-N transfer across PDV tissues. Energy corrected milk yield was greater with high NaCl compared with both control and feeding KCl, however, with KCl milk urea-N decreased.

Augmentation of Nitric Oxide Deficient Hypertension by High Salt Diet Is Associated With Reduced TNF-α Receptor Type 1 Expression in the Kidneys.

High salt (HS) intake induces an augmented hypertensive response to nitric oxide (NO) inhibition, though it causes minimal changes in blood pressure (BP) in NO intact condition. The cause of such augmentation is not known. HS induces tumor necrosis factor-alpha (TNFα) production that causes natriuresis via activation of its receptor type 1 (TNFR1). We hypothesized that NO deficiency reduces renal TNFR1 activity, leading to enhanced sodium retention and hypertension. We examined the changes in renal TNFR1 protein expression (Immunohistochemistry analyses) after HS (4% NaCl) intake in wild-type mice (WT, C57BL6) treated with a NO synthase (NOS) inhibitor, nitro-l-arginine methyl ester (L-NAME; 0.05 mg/min/g; osmotic mini-pump), as well as in endothelial NOS knockout mice (eNOSKO) and compared the responses in WT mice with normal salt (NS; 0.3% NaCl) intake. BP was measured with tail-cuff plethysmography and 24-hour urine collections were made using metabolic cages. HS alone did not alter mean BP in untreated mice (76 ± 3 to 77 ± 1 mm Hg) but induced an augmented response in L-NAME treated (106 ± 1 vs. 97 ± 2 mm Hg) and in eNOSKO (107 ± 2 vs. 89 ± 3 mm Hg) mice. The percentage area of TNFR1 expression in renal tissue was higher in WT + HS (4.1 + 0.5%) than in WT + NS mice (2.7 ± 0.6%). However, TNFR1 expression was significantly lower in L-NAME treated WT + NS (0.9 ± 0.1%) and in eNOSKO + NS (1.4 ± 0.2%) than in both WT + NS and WT + HS mice. These data indicate that TNFR1 activity is downregulated in NO deficient conditions, which facilitates salt retention leading to augmented hypertension during HS intake.

#1682 Myocardial remodeling in Wistar rats with renal dysfunction treated with a high-salt ration

Abstract Background and Aims High food intake of NaCl is the traditional factor of increase in blood pressure (BP) and cardiovascular risks also hurts kidneys. The purpose of the paper is to evaluate the morphological changes in the myocardium of normotensive Wistar rats with an early stage of renal dysfunction treated with a diet with increased concentration of salt for a long time. Method 30 Wistar rats (age 2.5-3 months) were studied and divided into three groups of 10 each. In the first, control, sham-operated (SO) rats, receiving standard diet (0.34% NaCl), in the second, rats subjected to resection of ¾ of the kidney parenchyma, receiving a standard diet (NE group), in the third, rats subjected to ¾ NE and those receiving a high-sodium diet (4% NaCl, high-salt diet, HSD). The feeds differed only in the %NaCl content. The ¾ NE model was created in two stages with an interval of 7 days. 20 mg/kg Zoletil 100 and 0.05 ml of Xylazine were used as anesthesia. At the first stage, the poles of the left kidney (1/2 part of the kidney) were removed, at the second stage, the right kidney was completely removed. The duration of the experiment was 4 months. At the end of the experiment, systolic BP at the tail was measured in awake rats using the cuff method (ELEMA electromanometer, Sweden). After removal from the experiment, blood was collected from the rats for biochemical analysis, and the LVMI was calculated as the ratio of LV mass to the body weight of the animal (mg/g). Myocardial fragments were placed in formalin, and sections 1.5–2 µm thick were prepared from paraffin blocks. The preparations were stained with Hematoxylin and Eosin and Masson's trichrome and used for histological analysis. The statistical significance of intergroup differences was determined using the Mann–Whitney test and Student's t test. Results During the observation period, BP in the SO group of animals did not change: initially - 120 [120;125] mm Hg, after 4 months - 120 [120;125] mmHg, p = 0.527. In the group with NE on a standard diet, an increase in BP was noted - from 120 [120; 125] mmHg up to 135.0 [132.5;137.5] mmHg, p = 0.011. In the group with NE + HSD, the increase in BP levels was more pronounced - up to 140[140;148] mmHg, (p = 0.001, relative to the SO group). The serum urea level in the SO group was 4.7 [4.5;5.4] mmol/l, creatinine −32.5 [29.0;36.0] µmol/l, in the NE group - 10.0 [9.1;10.9] mmol/l, (p = 0.0001, relative to the SO group) and 69.0[64.0;74.0] µmol/l, (p = 0.0001), in the NE+ HSD group – 10.7 [9.8;11.0] mmol/l, (p = 0.0001) and 64.5[46.3;69.5] µmol/l, (p = 0.001), respectively. Thus, the groups of rats with early-stage kidney dysfunction, although they had higher levels of urea and creatinine in the blood serum relative to the SO group, did not differ significantly from each other in these indicators. LVMI increased in rats with NE on a standard diet (LR −2.07±0.05 mg/g, NE −2.14 ± 0.06 mg/g, p = 0.1591). Consumption of a high-salt diet aggravated the growth of myocardial mass in rats with NE (NE + HSD - 2.41 ± 0.14 mg/g, p = 0.0084 and p = 0.0372, respectively). At the histological level, the increase in LV myocardial mass in rats with NE was characterized by hypertrophy of cardiomyocytes and the formation of interstitial fibrosis. The changes were more pronounced in the group with NE + HSD. The diameter of cardiomyocytes in rats of the SO group was 12.9 ± 0.4 µm, in animals with NE on standard diet - 14.5 ± 0.6 µm, in rats with NE + HSD - 15.5 ± 1.6 µm (p<0 .01 and p < 0.02, relative to the SO group). The area of interstitial fibrosis also increased in rats with NE (10.5 ± 2.6%, in the SO group - 0.6 ± 0.2%, p = 0.0000) and was slightly higher in the NE + HSD group (13.6 ± 2.8%, p = 0.0000, relative to the SO group). In rats with NE, both on a standard diet and with HSD, at this stage of the formation of kidney pathology, the thickness of the nutrimyocardial arteries did not differ significantly from the SO indicator rats. Conclusion Long-term salt intake with increased salt addition in Wistar rats in the initial stages of renal dysfunction does not affect the level of urea and creatinine in the blood serum, but promotes an increase in BP and myocardial remodeling, constantly progressing in the progression of cardiomyocyte hypertrophy and interstitial fibrosis.

Enhancing saltiness perception in bone broth: the additive effect of oil and optimization of sodium-reduction formula for consumer acceptability.

Excessive NaCl intake in liquid and semi-solid food (e.g. soup, hot pot base, sauce) poses a high risk to human health, and reducing NaCl intake is a major concern for global health. Using the generalized Labeled Magnitude Scale (gLMS) method, the study verified the possibility of sodium reduction through oil addition. The compromised acceptance threshold (CAT) and hedonic rejection threshold (HRT) were determined. The gLMS results showed that the saltiness intensity of samples containing 0.36% NaCl and 2.29% sunflower seed oil was significantly higher than that of samples containing only 0.36% NaCl (P < 0.05). CAT and HRT results indicated that by adding 3.59% sunflower oil, the NaCl content could be reduced to a minimum of 0.14% without causing sensory rejection in bone broth samples. The quantitative descriptive analysis method was used to determine the effects of NaCl and oil concentrations on the sensory attributes of bone broth samples. Furthermore, it was used to analyze the consumer acceptability drivers in combination with the hedonic scale to optimize the formulation of reduced-salt bone broth products. Notably, sample E (0.36% NaCl, 2.29% fat) not only had a significant salt reduction effect with a 20% decrease in NaCl, but also had improved overall acceptability. This study provides theoretical guidance for designing salt-reduction cuisine within the catering and food industries, including bone broth and hot pot bases. © 2024 Society of Chemical Industry.

Early Low-Grade Inflammation Induced by High-Salt Diet in Sprague Dawley Rats Involves Th17/Treg Axis Dysregulation, Vascular Wall Remodeling, and a Shift in the Fatty Acid Profile.

Unrestricted increased table salt (NaCl) intake is associated with oxidative stress and inflammation, leading to endothelial dysfunction and atherosclerosis. However, data on salt-induced immunomodulatory effects in the earliest phase of salt loading are scarce. In the present study, an animal model of short-term salt loading was employed, including male Sprague Dawley rats consuming a high-salt diet (HSD; 4% NaCl) or standard laboratory chow (low-salt; LSD; 0.4% NaCl) during a 7-day period. The contribution of angiotensin II (ANGII) suppression was tested by adding a group of rats on a high-salt diet receiving ANGII infusions. Samples of peripheral blood/mesenteric lymph node leukocytes, brain blood vessels, and serum samples were processed for flow cytometry, quantitative real-time PCR, total proteome analysis, and multiplex immunoassay. Data analysis revealed the up-regulation of Il 6 gene in the microcirculation of high-salt-fed rats, accompanied by an increased serum level of TNF-alpha cytokine. The high-salt diet resulted in increased proportion of serum mono-unsaturated fatty acids and saturated fatty acids, reduced levels of linoleic (C18:2 ω-6) and α-linolenic (C18:3 ω-3) acid, and increased levels of palmitoleic acid (C16:1 ω-7). The high-salt diet had distinct, lymphoid compartment-specific effects on leukocyte subpopulations, which could be attributed to the increased expression of salt-sensitive SGK-1 kinase. Complete proteome analysis revealed high-salt-diet-induced vascular tissue remodeling and perturbations in energy metabolism. Interestingly, many of the observed effects were reversed by ANGII supplementation. Low-grade systemic inflammation induced by a HSD could be related to suppressed ANGII levels. The effects of HSD involved changes in Th17 and Treg cell distribution, vascular wall remodeling, and a shift in lipid and arachidonic acid metabolism.

NaHCO3 loading causes increased arterial pressure and kidney damage in rats with chronic kidney disease.

Sodium bicarbonate (NaHCO3) is commonly utilized as a therapeutic to treat metabolic acidosis in people with chronic kidney disease (CKD). While increased dietary sodium chloride (NaCl) is known to promote volume retention and increase blood pressure, the effects of NaHCO3 loading on blood pressure and volume retention in CKD remain unclear. In the present study, we compared the effects of NaCl and NaHCO3 loading on volume retention, blood pressure, and kidney injury in both 2/3 and 5/6 nephrectomy remnant kidney rats, a well-established rodent model of CKD. We tested the hypothesis that NaCl loading promotes greater volume retention and increases in blood pressure than equimolar NaHCO3. Blood pressure was measured 24 h daily using radio telemetry. NaCl and NaHCO3 were administered in drinking water ad libitum or infused via indwelling catheters. Rats were housed in metabolic cages to determine volume retention. Our data indicate that both NaHCO3 and NaCl promote hypertension and volume retention in remnant kidney rats, with salt-sensitivity increasing with greater renal mass reduction. Importantly, while NaHCO3 intake was less pro-hypertensive than equimolar NaCl intake, NaHCO3 was not benign. NaHCO3 loading significantly elevated blood pressure and promoted volume retention in rats with CKD when compared with control rats receiving tap water. Our findings provide important insight into the effects of sodium loading with NaHCO3 in CKD and indicate that NaHCO3 loading in patients with CKD is unlikely to be benign.

Physiological and Molecular Responses of Pyrus pyraster Seedlings to Salt Treatment Analyzed by miRNA and Cytochrome P450 Gene-Based Markers.

Physiological and molecular marker-based changes were studied in the tissues of two-year-old Pyrus pyraster (L.) Burgsd. seedlings under salt treatment. For 60 days, 5 mL of 100 mM NaCl solution was applied to each plant per day to a cumulative volume of 300 mL in the substrate. In response to osmotic stress, the seedlings increased their water use efficiency (WUE) on day 20 of regular NaCl application and maintained a stable net photosynthetic rate (An) per unit area. Under conditions of increasing salinity, the young plants maintained a balanced water regime of the leaf tissues (Ψwl). The seedlings invested mass to their root growth (R/S), retained a substantial portion (72%) of Na+ ions in the roots, and protected their leaves against intoxication and damage. A significant decrease in the leaf gas exchange parameters (gs, E, An) was manifested on day 60 of the experiment when the cumulative NaCl intake was 300 mL per plant. The variability in the reactions of the seedlings to salinity is related to the use of open-pollinated progeny (54 genotypes) in the experiment. Lus-miR168 showed tissue- and genotype-specific genome responses to the applied stress. Polymorphic miRNA-based loci were mostly detected in the root samples on the 20th and 35th days of the experiment. The cumulative effect of the salt treatment was reflected in the predominance of polymorphic loci in the leaves. We can confirm that miRNA-based markers represent a sensitive detection tool for plant stress response on an individual level. The screening and selection of the optimal type of miRNA for this type of research is crucial. The cytochrome P450-Based Analog (PBA) techniques were unable to detect polymorphism among the control and treated seedlings, except for the primer pair CYP2BF+R, where, in the roots of the stressed plant, insertions in the amplicons were obtained. The expression ratios of cytochrome P450 in the salt-stressed plants were higher in the roots in the case of 20/100 mL and in the leaves with higher doses. The observed physiological and molecular responses to salinity reflect the potential of P. pyraster seedlings in adaptation to osmotic and ionic stress.

Estradiol modulation of behavioral and physiological body fluid control during repeated dietary sodium deprivation

The low salt diet is a first line treatment for hypertension, but it is a difficult diet to maintain. As a result, patients may alternate between periods of high and low salt intake, the effects of which are unclear. Importantly, blood pressure increases in women after menopause, suggesting that estrogen plays a role in preventing hypertension. At present, however, it is unknown if the behavioral and physiological impact of alternating episodes on the low salt diet may be altered by the presence of estrogen. Our goals were to assess salt intake and body fluid hormones with repeated dietary sodium deprivations. Using ovariectomized rats with (EB) and without (OIL) estrogen treatment, we subjected rats to one or two dietary sodium deprivations using low salt laboratory chow. 0.5 M NaCl and water intakes were recorded after each period of regular chow or deprivation. After deprivation, rats were sacrificed, and trunk blood was collected for analysis of vasopressin, norepinephrine, epinephrine, and aldosterone levels. Plasma sodium concentration, plasma protein concentration, body weight, and uterine weight were also measured. There was no difference in the salt intakes of OIL- or EB-treated rats after one or two dietary sodium deprivations. However, EB-treated rats drank a less concentrated solution overall, suggesting less overcompensation after dietary sodium deprivation. Additionally, after a single episode of dietary sodium deprivation, EB-treated rats’ consumption remained elevated above baseline even after returning to regular laboratory chow. These behavioral differences were not explained by alterations in vasopressin, norepinephrine, epinephrine, or aldosterone. Plasma sodium and plasma protein concentrations also did not show alterations related to the change in behavior. Further research is necessary to determine the mechanism behind these changes in intake in EB-treated rats, which may ultimately be clinically relevant for both pre- and postmenopausal women on the low salt diet.

High Salt Diet Exacerbates Intestinal Radiotoxicity by Promoting Intestinal Epithelial Barrier Dysfunction after RT

Intestinal side effects have a substantial impact on patients' quality of life and constrain radiation therapy (RT) of abdominal and pelvic tumors. We aim at gaining a better understanding of the pathogenesis of intestinal radiotoxicity and identifying contributing factors. A high salt diet is common among countries of the Global North. The effects of an increased sodium-chloride (NaCl) intake on the development of intestinal side effects have not been investigated. C57BL/6 wild-type (WT) mice were fed a high salt diet (HSD) or normal salt diet (NSD) and irradiated with 12 Gy total body irradiation (TBI) or 13 Gy abdominal irradiation (ABI). Following TBI the mice received a syngeneic bone marrow transplant to reconstitute hematopoiesis. Readouts after RT included weight monitoring, histopathological analysis and assessment of intestinal epithelial barrier function. To corroborate our findings in vitro, murine organoids of the small intestine were cultivated, treated with varying NaCl concentrations (110-200 mM) and irradiated with 2 or 4 Gy. Organoid survival and growth were determined using multiple methods. Additionally, colony formation assays (CFA) of murine MC38 colon carcinoma cells were performed after stimulation with NaCl. Mechanistically, we analyzed the apoptosis rates of MC38 cells and intestinal epithelial organoids. Irradiated HSD animals showed increased acute weight loss, reduced weight regeneration, a more severe dysfunction of the intestinal barrier (enhanced FITC-dextran permeability) and increased histopathological damage when compared with NSD animals. Murine intestinal organoids and MC38 cells showed decreased survival after RT in hypernatremic conditions. Interestingly, our preliminary data show that there are no increased rates of apoptotic cells in vitro, suggesting a different mechanism affecting the increased radiosensitivity in hypernatremic conditions. Our data show a NaCl induced intensification of intestinal tissue injury following RT. These findings can potentially pave the way for investigating the effect of high salt diet on intestinal radiotoxicity in clinical trials.

High Salt Promotes Inflammatory and Fibrotic Response in Peritoneal Cells.

Recent studies draw attention to how excessive salt (NaCl) intake induces fibrotic alterations in the peritoneum through sodium accumulation and osmotic events. The aim of our study was to better understand the underlying mechanisms. The effects of additional NaCl were investigated on human primary mesothelial cells (HPMC), human primary peritoneal fibroblasts (HPF), endothelial cells (HUVEC), immune cells (PBMC), as well as ex vivo on peritoneal tissue samples. Our results showed that a high-salt environment and the consequently increased osmolarity increase the production of inflammatory cytokines, profibrotic growth factors, and components of the renin-angiotensin-aldosterone system, including IL1B, IL6, MCP1, TGFB1, PDGFB, CTGF, Renin and Ace both in vitro and ex vivo. We also demonstrated that high salt induces mesenchymal transition by decreasing the expression of epithelial marker CDH1 and increasing the expression of mesenchymal marker ACTA2 and SNAIL1 in HPMCs, HUVECs and peritoneal samples. Furthermore, high salt increased extracellular matrix production in HPFs. We demonstrated that excess Na+ and the consequently increased osmolarity induce a comprehensive profibrotic response in the peritoneal cells, thereby facilitating the development of peritoneal fibrosis.

Physiological Mechanisms of Dietary Salt Sensing in the Brain, Kidney, and Gastrointestinal Tract.

Excess dietary salt (NaCl) intake is strongly correlated with cardiovascular disease and is a major contributing factor to the pathogenesis of hypertension. NaCl-sensitive hypertension is a multisystem disorder that involves renal dysfunction, vascular abnormalities, and neurogenically-mediated increases in peripheral resistance. Despite a major research focus on organ systems and these effector mechanisms causing NaCl-induced increases in arterial blood pressure, relatively less research has been directed at elucidating how NaCl is sensed by various tissues to elicit these downstream effects. The purpose of this review is to discuss how the brain, kidney, and gastrointestinal tract sense NaCl including key cell types, the role of NaCl versus osmolality, and the underlying molecular and electrochemical mechanisms.

Short Communication: The effect of exercise on salt intake by horses

Salt is a nutritional requirement for horses. The behavior patterns and physiological controls of salt (NaCl) intake were investigated. Camera traps were used to record visits to a salt block in a herd of pleasure horses of various breeds. There was a relation between the hours the horses were ridden per week and the number of times they licked salt over a 2-week period. The horses responded to exercise with an increase in salt intake. Owners should be aware that horses should have access to a salt block in order to meet the animals' physiological needs.

Urinary Calcium Is Associated with Serum Sclerostin among Stone Formers.

Sclerostin plays an important role in bone metabolism and adipose tissue. Animal studies suggest that sclerostin influences urinary calcium (UCa), but this relationship has not been evaluated in stone formers (SFs). We aimed to investigate the association of UCa with serum sclerostin, bone mineral density (BMD), and body composition among SFs. Clinical and laboratorial data were retrieved from medical records. Determinants of UCa were studied using linear regression. A total of 107 SFs (35.8 ± 9.3 years, 54% male) with eGFR 99.8 ± 14.5 mL/min/1.73 were studied. Subjects were split by sex and grouped into tertiles of UCa levels. Men in the highest UCa tertile had higher body mass index (BMI) and serum sclerostin, lower lean mass, and a trend towards higher fat mass. Women in the highest tertile had higher BMI and a trend towards higher serum sclerostin. Hypertension and metabolic syndrome, but not lower BMD, were more prevalent in the highest UCa tertile for both sexes. Sclerostin was positively correlated with fat mass and inversely correlated with lean mass among men, but not among women. BMD corrected for BMI at lumbar spine was inversely associated with UCa in a univariate analysis, but only serum sclerostin, hypertension, and NaCl intake were independent determinants of UCa in the multivariate model. The present findings disclose that in addition to hypertension and salt intake, serum sclerostin is associated with urinary calcium in stone formers, suggesting that in addition to the hormones traditionally thought to alter calcium reabsorption in the kidney, sclerostin may play a significant additional role, warranting further investigation.

Relationship Between High Sodium Chloride Intake and Obesity in Hypertensive Population A Cross-Sectional Study

Background: High Sodium chloride intake and obesity are significant, regarding hypertension in the population which may develop several medical complications. Objective: The aims and objectives of the current study were to introduce lifestyle medicine awareness in people for managing high blood pressure caused by high sodium chloride intake and obesity. Study Design: It was a cross-sectional clinical Study of the management of high blood pressure in a population with the help of nutrition &amp; physical exercise. Place and Duration: The present study was conducted from January to May 2023 and Patients were selected from the community health center and Ghurky Hospital Lahore. Methodology: ToA total of 10 of 0 hypertensive individuals were selected and divided into different groups regarding hypertension, obesity, sodium chloride intake in daily life, and other demographics. People were separated into different groups based on their sodium intake levels and BMI people were separated into different groups. In group- A there was 50 male and female while in group B other 50 male and female were included respectively. Results: Significant (P≤0.05) changes in systolic and diastolic blood pressure were seen in the individuals of both groups regarding NaCl intake. The mean standard deviation levels, BMI, Systolic and Diastolic blood pressure of men in Group-A and Group-B in the beginning (27.03±0.02, 130.01±0.01, 90.01±0.02), (30.01±0.02, 135.01±0.01, 90.01±0.02) after 15 days (27.03±0.02, 125.01±0.01, 83.01±0.01), (30.01±0.02, 140.01±0.01, 90.01±0.02) and after30 days (27.03±0.02, 124.01±0.01, 80.01±0.01), (30.01±0.02, 145.01±0.01, 100.01±0.01) were measured respectively. Similarly the mean standard deviation levels, BMI, Systolic and Diastolic blood pressure of women in Group-A and Group B in the beginning (28.03±0.02, 131.01±0.01, 88.01±0.02), (31.02±0.02, 131.01±0.01, 88.01±0.02) after 15 days (28.03±0.02, 125.01±0.01, 83.01±0.01), (31.02±0.02, 140.01±0.01, 90.01±0.02) and after30 days (28.03±0.02, 120.01±0.01, 84.01±0.01), (31.02±0.02, 150.01±0.01, 92.01±0.01) were calculated. Conclusion: All recommendations suggest limiting dietary salt as one of the tried-and-true ways to lower high blood pressure because there is a well-established link between excessive salt consumption and hypertension. A current study proved that high sodium chloride intake may increase blood pressure in humans. Keywords: Hypertensive, Sodium Chloride, BMI, Systolic and Diastolic blood pressure.

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.).

Continuous ingestion of sodium chloride solution promotes allergen absorption and may exacerbate allergy symptoms on ovalbumin-induced food allergy in mice.

Various studies have reported relationships between salt intake and diseases, such as hypertension, cardiovascular disease, stroke, gastric cancer, and bronchial asthma. However, no reports exist on the relationship between salt intake and food allergies. In this study, we investigated the effect of continuous ingestion of sodium chloride (NaCl) on allergy symptoms using a mouse model of food allergy. BALB/c mice were divided into four groups of 6-8 animals each. The control-water group (CW) and sensitization-water group (SW) groups were provided free access to water, and the control-1% NaCl group (CS) and sensitization-1% NaCl group (SS) groups were provided a 1% NaCl solution. The SW and SS groups were sensitized with 50 µg ovalbumin (OVA) at 2 timepoints by intraperitoneal injection. After oral administration of OVA, anaphylactic response was measured and blood was collected. The mice were sacrificed, and serum levels of OVA and anti-OVA immunoglobulin (Ig)E and IgG1 were measured by enzyme-linked immunosorbent assays. The sodium ion (Na+) concentrations in duodenal and jejunal extracts were measured using a Na+ ion meter. The results suggested that continuous ingestion of a 1% NaCl solution for 36 days promoted allergen absorption and may have aggravated allergy symptoms in the mice. However, NaCl ingestion did not affect Na+ concentrations in the small intestine or OVA-specific antibody production.

Sodium Homeostasis, a Balance Necessary for Life.

Body sodium (Na) levels must be maintained within a narrow range for the correct functioning of the organism (Na homeostasis). Na disorders include not only elevated levels of this solute (hypernatremia), as in diabetes insipidus, but also reduced levels (hyponatremia), as in cerebral salt wasting syndrome. The balance in body Na levels therefore requires a delicate equilibrium to be maintained between the ingestion and excretion of Na. Salt (NaCl) intake is processed by receptors in the tongue and digestive system, which transmit the information to the nucleus of the solitary tract via a neural pathway (chorda tympani/vagus nerves) and to circumventricular organs, including the subfornical organ and area postrema, via a humoral pathway (blood/cerebrospinal fluid). Circuits are formed that stimulate or inhibit homeostatic Na intake involving participation of the parabrachial nucleus, pre-locus coeruleus, medial tuberomammillary nuclei, median eminence, paraventricular and supraoptic nuclei, and other structures with reward properties such as the bed nucleus of the stria terminalis, central amygdala, and ventral tegmental area. Finally, the kidney uses neural signals (e.g., renal sympathetic nerves) and vascular (e.g., renal perfusion pressure) and humoral (e.g., renin-angiotensin-aldosterone system, cardiac natriuretic peptides, antidiuretic hormone, and oxytocin) factors to promote Na excretion or retention and thereby maintain extracellular fluid volume. All these intake and excretion processes are modulated by chemical messengers, many of which (e.g., aldosterone, angiotensin II, and oxytocin) have effects that are coordinated at peripheral and central level to ensure Na homeostasis.

S-51-6: RENOVASCULAR HYPERTENSION AND BRAIN: ROLE OF THE RENIN-ANGIOTENSIN SYSTEM AND SODIUM

Renovascular hypertension is a type of secondary hypertension. Renovascular hypertensive 2-kidney, 1-clip (2K1C) rats have an increased activity of the renin-angiotensin system, and it is an experimental model to study renovascular hypertension. Renovascular hypertensive 2K1C rats have an imbalance of RAS components in the brain, an impairment of the baroreflex and they present an increase in daily intake of hypertonic NaCl solution. Therefore, we focused on studying: 1) the effects of overexpression of RAS components in the in the nucleus of the solitary tract (NTS), a brainstem area involved with cardiovascular control, 2) the brain mechanisms involved with the sodium appetite (operationally defined as an ingestion of hypertonic NaCl solution) in 2K1C rats. In adult Holtzman rats, the left renal artery was partially occluded by a silver clip with an opening of 0.2 mm to induce 2K1C. The experiments started after 6 weeks (hypertension plateau). We observed that increasing angiotensin type 2 receptor (AT2R) expression in the NTS attenuated the development of renovascular hypertension and also reversed the impairment of the baroreflex observed in 2K1C rats. Furthermore, an observed decrease in mRNA levels of angiotensin-converting enzyme 2 in the NTS of 2K1C rats was restored to control levels after viral-mediated increases in AT2R at this site. Virally mediated blockade of an intracellular pathway activated by angiotensin II (ANG II) acting in type 1 receptor (AT1R) in the NTS attenuated the development of renovascular hypertension and also reversed the impairment of the baroreflex. Daily 0.3 M NaCl intake transiently increased from the 2nd to the 5th week after 2K1C surgery. On the 6th week, in spite of comparable daily 0.3 M NaCl intake between 2K1C and sham rats, water deprivation (used to induce sodium appetite) produced a greater increase 0.3 M NaCl intake in 2K1C rats. Moreover, this intake is totally blocked by central AT1R and mineralocorticoid receptor antagonism. These data demonstrated that ANG II acting in the AT1R in the NTS is involved with the development of hypertension and baroreflex impairment in 2K1C and that AT2 overexpression at the same site can counteract these effects. In addition, the results demonstrated the participation of ANG II and aldosterone acting centrally in the enhanced sodium intake in water deprived 2K1C rats.

PL-4: INSIGHTS INTO MOLECULAR MECHANISMS OF HYPERTENSION FROM HUMAN GENETICS

Identification and investigation of rare patients with extreme forms of high and low blood pressure has led to the identification of specific genes whose mutation results in these outlier phenotypes. These rare mutations converge on genes that mediate or regulate the renal reabsorption of Na-Cl. Mutations that increase or decrease renal salt reabsorption respectively increase or decrease blood pressure. Mutations that cause hypertension include gain of function mutations in subunits of the epithelial Na+ channel (ENaC) and in any of eight genes that cause constitutive activity of ENaC by its stimulation via its major regulator, the mineralocorticoid receptor, the target of aldosterone signaling; these increase salt reabsorption in the distal nephron. Conversely, mutations that cause hypotension include loss of function mutations in ENaC subunits, but also mutations the thiazide-sensitive Na-Cl cotransporter (NCC) or a K+ channel required for cotransporter function that act in the distal convoluted tubule (DCT), or mutations in the Na-K-2Cl cotransporter as well as K+ and Cl- channels expressed in the thick ascending limb of Henle that are required for normal Na-Cl reabsorption in this nephron segment. ENaC, the Na-Cl cotransporter and the Na-K-2Cl cotransporter, as well as the mineralocorticoid receptor are all commonly used targets for treatment of hypertension and/or diuresis. In addition to these genes, genetic studies also identified a previously unrecognized pathway that regulates the balance between renal salt reabsorption and K+ secretion. Mutations in the kinases WNK1 or WNK4, or genes that mediate their degradation via ubiquitylation, CUL3 and KLHL3 cause hypertension with hyperkalemia. Activity of WNK1 and WNK4 stimulates activation of NCC promoting Na-Cl reabsorption in the DCT, reducing Na-Cl- delivery distally, thereby limiting ENaC activity and limiting K+ secretion in the distal nephron. Conversely, hyperkalemia inhibits WNK activity, promoting distal Na-Cl delivery and maximizing K+ secretion. Angiotensin II signaling promotes WNK activity, increasing Na-Cl reabsorption in the DCT and inhibiting K+ secretion, while hyperkalemia appears to inhibit WNK activity, providing distal Na+ delivery that is used to drive K+ secretion. The importance of this pathway is that it can explain the mechanism by which increased dietary K+ lowers blood pressure. Both reduced dietary salt intake and increased dietary K+ can reduce blood pressure in controlled settings, and recent large population studies have shown that increased dietary K+ and reduced Na-Cl intake not only lower blood pressure but reduce the incidence of cardiovascular disease and death.