High Salt Intake Research Articles

Conventional Vasopressor and Vasopressor-Sparing Strategies to Counteract the Blood Pressure-Lowering Effect of Small Interfering RNA Targeting Angiotensinogen.

BackgroundA single dose of small interfering RNA (siRNA) targeting liver angiotensinogen eliminates hepatic angiotensinogen and lowers blood pressure. Angiotensinogen elimination raises concerns for clinical application because an angiotensin rise is needed to maintain perfusion pressure during hypovolemia. Here, we investigated whether conventional vasopressors can raise arterial pressure after angiotensinogen depletion.Methods and ResultsSpontaneously hypertensive rats on a low‐salt diet were treated with siRNA (10 mg/kg fortnightly) for 4 weeks, supplemented during the final 2 weeks with fludrocortisone (6 mg/kg per day), the α‐adrenergic agonist midodrine (4 mg/kg per day), or a high‐salt diet (all groups n=6–7). Pressor responsiveness to angiotensin II and norepinephrine was assessed before and after siRNA administration. Blood pressure was measured via radiotelemetry. Depletion of liver angiotensinogen by siRNA lowered plasma angiotensinogen concentrations by 99.2±0.1% and mean arterial pressure by 19 mm Hg. siRNA‐mediated blood pressure lowering was rapidly reversed by intravenous angiotensin II or norepinephrine, or gradually reversed by fludrocortisone or high salt intake. Midodrine had no effect. Unexpectedly, fludrocortisone partially restored plasma angiotensinogen concentrations in siRNA‐treated rats, and nearly abolished plasma renin concentrations. To investigate whether this angiotensinogen originated from nonhepatic sources, fludrocortisone was administered to mice lacking hepatic angiotensinogen. Fludrocortisone did not increase angiotensinogen in these mice, implying that the rise in angiotensinogen in the siRNA‐treated rats must have depended on the liver, most likely reflecting diminished cleavage by renin.ConclusionsIntact pressor responsiveness to conventional vasopressors provides pharmacological means to regulate the blood pressure–lowering effect of angiotensinogen siRNA and may support future therapeutic implementation of siRNA.

The Association of Salt Intake and Non-alcoholic Fatty Liver Disease in People With Type 2 Diabetes: A Cross-Sectional Study.

ObjectivesNon-alcoholic fatty liver disease (NAFLD), which has a close relationship with type 2 diabetes (T2D), is related to salt intake in the general population. In contrast, the relationship between salt intake and the presence of NAFLD in patients with T2D has not been clarified.MethodsSalt intake (g/day) was assessed using urinary sodium excretion, and a high salt intake was defined as an intake greater than the median amount of 9.5 g/day. Hepatic steatosis index (HSI) ≥ 36 points was used to diagnosed NAFLD. Odds ratios of high salt intake to the presence of NAFLD were evaluated by logistic regression analysis.ResultsThe frequency of NAFLD was 36.5% in 310 patients with T2D (66.7 ± 10.7 years old and 148 men). The patients with high salt intake had a higher body mass index (25.0 ± 4.0 vs. 23.4 ± 3.8 kg/m2, p < 0.001) than those with low salt intake. HSI in patients with high salt intake was higher than that in patients with low salt intake (36.2 ± 6.2 vs. 34.3 ± 5.5 points, p = 0.005). In addition, the presence of NALFD in patients with high salt intake was higher than that in patients with low salt intake (44.5% vs. 28.4%, p = 0.005). High salt intake was associated with the prevalence of NAFLD [adjusted odds ratio, 1.76 (95% confidence interval: 1.02–3.03), p = 0.043].ConclusionThis cross-sectional study revealed that salt intake is related to the prevalence of NAFLD in patients with T2D.

Prevalence of Health-Risk Behaviors and Mental Well-Being of ASEAN University Students in COVID-19 Pandemic.

The prevalence of epidemiological health-risk behaviors and mental well-being in the COVID-19 pandemic, stratified by sociodemographic factors in Association of South East Asian Nations (ASEAN) university students, were examined in the research. Data were collected in March–June 2021 via an online survey from 15,366 university students from 17 universities in seven ASEAN countries. Analyzed data comprised results on physical activity, health-related behaviors, mental well-being, and sociodemographic information. A large proportion of university students consumed sugar-sweetened beverages (82.0%; 95%CI: 81.4, 82.6) and snacks/fast food daily (65.2%; 95%CI: 64.4, 66.0). About half (52.2%; 95%CI: 51.4, 53.0) consumed less than the recommended daily amounts of fruit/vegetable and had high salt intake (54%; 95%CI: 53.3, 54.8). Physical inactivity was estimated at 39.7% (95%CI: 38.9, 40.5). A minority (16.7%; 95%CI: 16.1, 17.3) had low mental well-being, smoked (8.9%; 95%CI: 8.4, 9.3), and drank alcohol (13.4%; 95%CI: 12.8, 13.9). Country and body mass index had a significant correlation with many health-risk behaviors and mental well-being. The research provided important baseline data for guidance and for the monitoring of health outcomes among ASEAN university students and concludes that healthy diet, physical activity, and mental well-being should be key priority health areas for promotion among university students.

Role of inwardly rectifying K+ channel 5.1 (Kir5.1) in the regulation of renal membrane transport.

Kir5.1 interacts with Kir4.2 in proximal tubule and with Kir4.1 in distal convoluted tubule (DCT), connecting tubule (CNT) and cortical collecting duct (CCD) to form basolateral-K+-channels. Kir4.2/Kir5.1 and Kir4.1/Kir5.1 play an important role in regulating Na+/HCO3--transport of the proximal tubule and Na+/K+ -transport in the DCT/CNT/CCD. The main focus of this review is to provide an overview of the recent development in the field regarding the role of Kir5.1 regulating renal electrolyte transport in the proximal tubule and DCT. Loss-of-function-mutations of KCNJ16 cause a new form of tubulopathy, characterized by hypokalaemia, Na+-wasting, acid-base-imbalance and metabolic-acidosis. Abnormal bicarbonate transport induced by loss-of-function of KCNJ16-mutants is recapitulated in Kir4.2-knockout-(Kir4.2 KO) mice. Deletion of Kir5.1 also abolishes the effect of dietary Na+ and K+-intakes on the basolateral membrane voltage and NCC expression/activity. Long-term high-salt intake or high-K+-intake causes hyperkalaemic in Kir5.1-deficient mice. Kir4.2/Kir5.1 activity in the proximal tubule plays a key role in regulating Na+, K+ and bicarbonate-transport through regulating electrogenic-Na+-bicarbonate-cotransporter-(NBCe1) and type 3-Na+/H+-exchanger-(NHE3). Kir4.1/Kir5.1 activity of the DCT plays a critical role in mediating the effect of dietary-K+ and Na+-intakes on NCC activity/expression. As NCC determines the Na+ delivery rate to the aldosterone-sensitive distal nephron (ASDN), defective regulation of NCC during high-salt and high-K+ compromises renal K+ excretion and K+ homeostasis.

Association between Perceived Salt Intake and Arterial Stiffness.

To explore the association of perceived salt intake (SI) level with arterial stiffness in the community population in northern China. We enrolled participants who completed the health questionnaire, physical examination, and brachial-ankle pulse wave velocity (baPWV) test during 2010-2019 and divided them into <6 g (low SI), 6-10 g (medium SI), and >10 g (high SI) groups based on their daily SI. The influence of SI on baPWV was analyzed using the multivariate logistic regression model. A total of 36324 subjects, aged (49.10 ± 12.57) years with a male to female ratio of 25934 : 10390, met the inclusion criteria and were enrolled. The average baPWV was (1527.73 ± 355.61) cm/s. Logistic regression analysis showed that after adjusting for other confounders, daily SI>10 g (high SI) was a risk factor for arterial stiffness (baPWV ≥1400 cm/s), with the odds ratio (95% confidence interval [CI]) of 1.17 (1.04-1.31). High SI is independently associated with arterial stiffness.

Prevalence of noncommunicable diseases risk factors and their determinants in Malawi

Introduction: By 2030, the noncommunicable diseases (NCDs) are expected to overtake communicable, maternal, neonatal, and nutritional diseases combined as the leading cause of mortality in sub-Saharan Africa. With the increasing trend in NCDs, the NCD risk factors (NCDRF) need to be understood at local level to guide NCD risk mitigation efforts. Therefore, we provide a detailed analysis of some modifiable NCDRF and their determinants in Malawi using the 2017 Stepwise survey (STEPS). Methods: This is a secondary analysis of the Malawi 2017 STEPS. Data were analyzed using frequencies, proportions, odds ratios, and their associated 95% confidence intervals (95%CI). We fitted multiple logistic regression of the NCDRF on the explanatory variables using the likelihood ratio test. The level of statistical significance was set at P &lt; 0.05. Results: Of the 4187 persons, 9% were current smokers, 1% were taking alcohol, 16% had a high salt intake, 64% had insufficient fruit intake, 21% had low physical activity, 25% had high blood sugar, and 11% had high blood pressure. Smoking odds increased with age but decreased with the level of education. Females had lower odds of engaging in harmful alcohol use than males (adjusted odds ratio [AOR] = 0.04, 95%CI: 0.01–0.17, P &lt; 0.001). Females had lower odds of high salt uptake than the males (AOR = 0.70, 95%CI: 0.58–0.84, P = 0.0001). Persons in nonpaid jobs had higher odds of salt uptake than those employed (AOR = 1.70, 95%CI: 1.03–2.79, P = 0.04). Females were 22% more likely to have insufficient fruit uptake compared to males (AOR = 1.22, 95%CI: 1.06–1.41, P = 0.007). Conclusion: The high prevalence of physical inactivity, high salt consumption, insufficient fruit intake, raised blood glucose and high relative blood pressure calls for a sound public health approach. The Malawi Ministry of Health should devise multisectoral approaches that minimize exposure to modifiable NCDRF at population and individual levels.

A Gastric Adenocarcinoma Case Presenting with Hematuria

Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Risk factors for gastric cancer include Helicobacter pylori infection, advanced age, familial history of gastric cancer, high salt intake, and a diet

Alleviation of Metabolic Disturbance by Substituting Kanjang High in Bacillus for Salt through Modulation of Gut Microbiota in Estrogen-Deficient Rats.

A high salt intake may exacerbate menopausal symptoms and substituting for different types of traditionally made kanjang (TMK; soy sauce) may prevent it. This study examined whether substituting salt with lyophilized TMK containing low and high Bacillus and biogenic amines in a high-fat diet might modulate the menopausal symptoms and the energy, glucose, and lipid metabolism in ovariectomized (OVX) rats. They were categorized into salt (Control), TMK with high Bacillus and low biogenic amines (HBLB), TMK with high Bacillus and high biogenic amines (HBHB), TMK with low Bacillus and low biogenic amines (LBLB), and TMK with low Bacillus and high biogenic amines (LBHB). Sham-operated rats consumed the same diet as the Control. HBLB, HBHB, and LBHB prevented increased tail skin temperature compared to the Control. HBHB and HBLB partially inhibited the increased weight gain and abdominal fat mass by reducing the food efficiency without changing the serum 17β-estradiol concentrations. Serum glucose and insulin concentrations and the insulin resistance index by the homeostatic model assessment for insulin resistance showed a positive association for weight gain. HBLB and HBHB decreased the serum malondialdehyde and tumor-necrosis factor-α levels. Hepatic triglyceride storage was lower in all TMK groups than in the Control, while hepatic glycogen accumulation was higher in the HBLB, HBHB, and LBHB groups than in the Control and LBLB groups. Accordingly, the mRNA expression of peroxisome proliferator-activated receptors-γ(PPAR-γ) was higher in the HBLB and HBHB groups compared to the Control, and that of fatty acid synthase was opposite to PPAR-γ expression. However, HBLB and HBHB improved dyslipidemia and insulin resistance compared to the Control, but their improvement did not reach that of the Normal-control. The acetic acid concentrations in the portal vein were lower in the LBLB than in the Control, while the butyric acid contents were higher in the LBHB and HBLB groups than in the Control. HBHB, HBLB, and LBHB elevated Akkermansia and Lactobacillus, and HBLB and LBLB increased Bacteroides and Ruminococcus compared to the Control. Polycyclic aromatic hydrocarbon degradation, bile acid synthesis, and unsaturated fatty acid biosynthesis were significantly higher in the HBLB group than in the Control group. In conclusion, substituting salts to TMK with a high Bacillus content regardless of the bioamine contents partially improved the menopausal symptoms and metabolic disturbance in estrogen-deficient animals.

The Jamaica salt consumption, Knowledge, Attitudes and Practices (Salt-KAP) study: A research protocol

Background: Excess dietary salt consumption is a major contributor to hypertension and cardiovascular disease. Public education programs on the dangers of high salt intake, and population level interventions to reduce the salt content in foods are possible strategies to address this problem. In Jamaica, there are limited data on the levels of salt consumption and the population’s knowledge and practices with regards to salt consumption. This study therefore aims to obtain baseline data on salt consumption, salt content in foods sold in restaurants, and evaluate knowledge, attitudes, and practices of Jamaicans regarding salt consumption. Methods: The study is divided into four components. Component 1 will be a secondary analysis of data on urinary sodium from spot urine samples collected as part of a national survey, the Jamaica Health and Lifestyle Survey 2016-2017. Component 2 will be a survey of chain and non-chain restaurants in Jamaica, to estimate the sodium content of foods sold in restaurants. Component 3 is another national survey, this time on a sample 1,200 individuals to obtain data on knowledge, attitudes and practices regarding salt consumption and estimation of urinary sodium excretion. Component 4 is a validation study to assess the level of agreement between spot urine sodium estimates and 24-hour urinary sodium from 120 individuals from Component 3. Discussion: This study will provide important baseline data on salt consumption in Jamaica and will fulfil the first components of the World Health Organization SHAKE Technical Package for Salt Reduction. The findings will serve as a guide to Jamaica’s Ministry of Health and Wellness in the development of a national salt reduction program. Findings will also inform interventions to promote individual and population level sodium reduction strategies as the country seeks to achieve the national target of a 30% reduction in salt consumption by 2025.

A Mobile Phone App Intervention to Promote Healthy Salt Intake Among Adults: Protocol for a Randomized Controlled Study.

BackgroundThere is sound evidence associating high salt intake and a greater risk of cardiovascular and noncardiovascular diseases. High salt intake has been observed in several populations worldwide. Therefore, promoting healthier salt consumption has been encouraged as a low-cost strategy to reduce this risk factor. However, these strategies need to be sound, built on theoretical and methodological bases, and consider the target population’s context.ObjectiveThis protocol aims to describe a mobile phone app intervention to promote healthy salt intake among adults.MethodsThis is an experimental and longitudinal study protocol conducted in three modules. Module 1 refers to the planning of the intervention based on the Behaviour Change Wheel framework. Module 2 is the development of the mobile phone app intervention based on the date of module 1. In module 3, the intervention will be evaluated using a randomized controlled study, with three steps of data collection in a 2-month follow-up in a sample of 86 adults (43 participants for each group: the control group and intervention group) recruited from the primary health care centers of a Brazilian town. The discretionary salt intake questionnaire will assess salt consumption, the app usability will be assessed using the System Usability Scale, and psychosocial variables (habit, intention, and self-efficacy) will also be measured.ResultsRecruitment began in October 2021, and the follow-up will end in August 2022. The results of this study are expected to be published in 2023.ConclusionsResults from this study will help people to control salt intake when cooking at home, will stimulate self-care, will work as an alternative or supportive method in the relationship between health care professionals and patients, and will contribute to implementing the app intervention to promote healthy salt intake on a large scale.Trial RegistrationThe Brazilian Clinical Trials Registry RBR-4s8qyyq; https://ensaiosclinicos.gov.br/rg/RBR-4s8qyyqInternational Registered Report Identifier (IRRID)DERR1-10.2196/37853

Combined Risks of Hyperlipidemia and Hypertension for Coronary Heart Disease: A Case-Control Study of the Local Population of Bahawalpur, Pakistan

Hypercholesterolemia, being one of the most important risk factors for coronary heart disease, is defined as a total cholesterol concentration of ≥240 mg/dL. Hypertension has become a major public health hazard all over the world due to the serious damage it causes to the body organs and the many complications it induces, including the coronary heart disease. The current study aimed to evaluate the combined risks of correlation between hypertension and hyperlipidemia and their association with coronary heart disease. It included 100 patients diagnosed with hypertension and hyperlipidemia, as well as 100 healthy individuals of the same age and background. A standardized questionnaire was used to collect the family history of patients and control. Blood samples with a volume of 3-5ml were drawn from all patients to analyze the composition of blood serum including LDL (low-density lipoprotein), HDL (high-density lipoprotein), triglyceride, and cholesterol levels. The frequencies of all concerned factors were calculated and the mean values of blood pressure, cholesterol, LDL, and HDL were found to be in the hazardous range in patients. The data were analyzed using the chi-square test and binomial regression statistical analysis. The analysis of risk factors revealed that age, BMI (body mass index), high blood pressure, smoking, and high salt intake had a significant association with the high lipid profile in the patients. The risk of cardiovascular diseases (CVDs) is enhanced in patients with high blood pressure and hyperlipidemia.

The association between salt intake and blood pressure is mediated by body mass index but modified by hypertension: The ELSA-Brasil study.

High salt intake has been linked to both obesity and high blood pressure (BP). Part of the variability of BP attributed to salt intake might be BMI-mediated. To investigate whether hypertension would be an effect modifier in the complex network including salt intake, obesity, and BP, we tested the hypothesis that salt intake has direct and BMI-mediated effects on systolic (SBP) and diastolic blood pressure (DBP). Data from 9,028 participants (aged 34-75 years, 53.6% women) were analyzed. A validated formula was used to estimate daily salt intake from the sodium excretion (12 h urine collection). A path model adjusted for covariates was designed in which salt intake has both a direct and a BMI-mediated effect on BP. In normotensives, standardized beta coefficients showed significant direct (Men: 0.058 and 0.052, Women: 0.072 and 0,061, P < 0.05) and BMI-mediated (Men: 0.040 and 0.065, Women: 0.038 and 0.067, P < 0.05) effect of salt intake on the SBP and DBP, respectively. However, in hypertensive individuals, neither the direct (Men: 0.006 and 0.056, Women: 0.048 and 0.017) nor the indirect effect (Men: -0.044 and 0.014, Women: 0.011 and 0.050) of salt intake on the SBP and DBP were significant. These data suggest that cardiovascular risk stratification should consider the complex interaction between salt intake and weight gain, and their effects on BP of normotensive and hypertensive individuals.

Salt as a Trigger for Atrial Tachycardia/Fibrillation

A variety of potential triggers of atrial fibrillation (AF) have been reported, including alcohol consumption, caffeine, exercise, and stress. Vagal AF triggers include gastrointestinal factors such as the amount of food consumed, types of foods, and gas and bloating. In this case report, detailed data of seven dietary and behavioral factors (many vagal) believed to be possible atrial tachycardia (AT) or AF triggers in a single patient with paroxysmal AT/AF were recorded. Episodes of AT and AF were recorded in the patient using a Medtronic loop recorder and analyzed by a cardiac electrophysiologist. To evaluate these potential triggers of AT/AF events, a general linear model with binomial family error distribution was used to fit the data. Then, a stepAIC function from the MASS package in R was used to perform a stepwise model selection using AIC (Akaike information criterion). The analysis only identified the amount of salt intake and the use of polyethylene glycol 3350 as predictors of AT/AF, and high salt intake was the only factor significantly associated with the onset of AT/AF (P < 0.05). Thus, salt intake may trigger AT/AF in ways other than via hypertension.

Momordica charantiaExtract Confers Protection Against Hypertension in Dahl Salt-Sensitive Rats.

Hypertension is one of the main factors of cardiovascular disease worldwide and is strongly related to the overall mortality. High salt intake is a major risk factors for hypertension. Identifying functional foods that can help prevent mechanistic abnormalities mediating salt-induced hypertension is an issue of considerable nutraceutical and scientific interest. Dietary Momordica charantia may be an alternative approach to avoid salt-induced hypertension. Dahl salt-sensitive (DSS) rats were used to determine whether Momordica charantia water extracts (ME) exerts anti-hypertensive effects in the present study. ME gavage could significantly prevented the increase of blood pressure, blood urea nitrogen, creatinine, and urine protein-to-creatinine ratio of DSS rats. Metabolomics analysis indicated that high-salt diet induced abnormal amino acid metabolism was related to nitric oxide (NO) deficiency, but ME gavage could upregulate the activities of nitric oxide synthase, aspartate aminotransferase, argininosuccinate lyase, argininosuccinate synthase and restore endogenous synthesis of arginine and NO. Meanwhile, renal function was improved after ME gavage. Citrulline, as one of the important component in ME, could attenuate salt-induced hypertension by increasing endogenous synthesis of arginine and NO. Antioxidants in ME, such as phenolic compound, may avoid high-salt induced oxidative stress in DSS rats, which may be another mechanism by which ME prevented blood pressure increase. Thus, the present study indicated that feeding Momordica charantia could avoid high-salt-induced hypertension in DSS rats.

Abstract 737: Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort

Abstract Background: Certain diet components (i.e. low intake of fruit/vegetables and high intake of salt and processed meats) have been associated with risk of gastric cancer. However, it is unclear whether overall diet quality assessed by pre-defined indices, that take into account the complexity of dietary intake, is associated with gastric cardia and distal adenocarcinoma particularly in a racially and ethnically diverse population. Our objectives are to 1) examine the association of a variety of diet quality indices with risk of gastric cardia and distal adenocarcinoma and 2) assess if there are any subgroups that may benefit from better diets to reduce risk of gastric adenocarcinoma. Methods: The analysis included 176,752 men and women aged 45-75 from the Multiethnic Cohort (MEC), who were African American, Japanese American, Latino, Native Hawaiian, or White, and completed a quantitative food frequency questionnaire (QFFQ) at cohort entry. Incident cases of gastric cancer (cardia ICD-O-3 C16.0 and non-cardia adenocarcinoma C16.1-C16.6) were identified by linkages with the Surveillance, Epidemiology, and End Results (SEER) cancer registries. Dietary indices, Alternative Healthy Index-2010 (AHEI-2010), Healthy Eating Index-2015 (HEI-2015), Dietary Approach to Stop Hypertension (DASH) score, alternate Mediterranean Diet (aMED) score, and Dietary Inflammatory Index (DII®), were calculated from the QFFQ and categorized into quintiles. Multivariable Cox models were used to estimate the association between dietary indices and gastric cancer risk by anatomic site. Effect modification was assessed for distal cancer by sex, smoking status, and aspirin use. Results: A total of 207 incident cases of gastric cardia and 836 incident cases of gastric non-cardia were identified during an average follow up of 19.2 years. We did not observe any significant associations between any of the dietary indices and gastric cancer for both cardia and non-cardia tumors. However, we observed effect modification by aspirin use for aMED (P for heterogeneity = 0.01) as well as for DII (P for heterogeneity = 0.02). Among ever aspirin users, we observed an inverse association between aMED (HRQ5 vs Q1: 0.82, 95% CI: 0.53-1.26, Ptrend = 0.03) with non-cardia cancer, and the association with DII® was borderline statistically significant for the trend test (HRQ5 vs Q1: 0.86, 95% CI: 0.57-1.29, Ptrend = 0.07). Conclusion: In a multiethnic population, we did not observe overall significant associations between these dietary quality indices and risk of gastric cancer. However, among ever aspirin users there could be a reduction of gastric non-cardia adenocarcinoma risk with a higher adherence to a Mediterranean diet. Citation Format: Nicholas Acuna, Song-Yi Park, Anna H. Wu, Lynne R. Wilkens, V. Wendy Setiawan. Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 737.

Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na+/H+ Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway.

Background:The present study directly tested the crucial role of intestinal gastrin/CCKBR (cholecystokinin B receptor) in the treatment of salt-sensitive hypertension.Methods:Adult intestine-specific Cckbr-knockout mice (Cckbrfl/fl villin-Cre) and Dahl salt-sensitive rats were studied on the effect of high salt intake (8% NaCl, 6–7 weeks) on intestinal Na+/H+ exchanger 3 expression, urine sodium concentration, and blood pressure. High-salt diet increased urine sodium concentration and systolic blood pressure to a greater extent in Cckbrfl/fl villin-Cre mice and Dahl salt-sensitive rats than their respective controls, Cckbrfl/fl villin mice and SS13BN rats. We constructed gastrin-SiO2 microspheres to enable gastrin to stimulate specifically and selectively intestinal CCKBR without its absorption into the circulation.Results:Gastrin-SiO2 microspheres treatment prevented the high salt-induced hypertension and increase in urine Na concentration by inhibiting intestinal Na+/H+ exchanger 3 trafficking and activity, increasing stool sodium without inducing diarrhea. Gastrin-mediated inhibition of intestinal Na+/H+ exchanger 3 activity, related to a PKC (protein kinase C)-mediated activation of NHERF1 and NHERF2.Conclusions:These results support a crucial role of intestinal gastrin/CCKBR in decreasing intestinal sodium absorption and keeping the blood pressure in the normal range. The gastrointestinal administration of gastrin-SiO2 microspheres is a promising and safe strategy to treat salt-sensitive hypertension without side effects.

SHORT-TERM HIGH SALT INTAKE ADVERSELY AFFECTS PARAMETERS DERIVED FROM RESERVOIR-EXCESS PRESSURE ANALYSIS AND CENTRAL ARTERY HAEMODYNAMICS IN OVERWEIGHT/OBESE ADULTS

Objective: The association between high salt intake and blood pressure is well-recognised. In overweight/obese individuals, obesity-associated hyperinsulinaemia augments renal sodium reabsorption and in combination with high salt intake this may alter blood pressure and arterial haemodynamics. We determined whether short-term high salt intake altered reservoir-excess pressure and central artery haemodynamic parameters in overweight/obese individuals. Design and method: We studied 15 middle-aged and older adults (59.3 ± 6.4 yrs, 5F) who were overweight/obese with elevated systolic blood pressure (130 &lt; SBP &lt; 159 mmHg). In a double-blind cross-over design, they were randomly assigned to seven days of low salt diet (LSD: 50 mmol/day) or high salt intake (HIS: LSD with 200 mmol/day of sodium tablets) separated by a two-week washout period. The parameters derived from reservoir-excess pressure analysis including reservoir pressure integral, peak reservoir pressure (MAXPR), excess pressure integral (INTXSP), peak excess pressure (MAXXSP), systolic rate constant and diastolic rate constant (DRC) were obtained by radial artery tonometry. Additionally central artery haemodynamic parameters including aortic systolic pressure (aSBP), diastolic pressure (aDBP), pulse pressure (aPP) and subendocardial viability index (SVI) were derived from ensemble-averaged radial pulse waveform using generalised transfer function. Aortic pulse wave velocity (aPWV) was estimated as proposed by Hughes et al (Front Physiol. 2020). Results: MAXPR (111.0 ± 10.9 vs 105.4 ± 10.4 mmHg), MAXXSP (41.7 ± 12.0 vs 36.6 ± 5.7 mmHg) and DRC (2.0 ± 0.4 vs 1.8 ± 0.3 s-1) were higher following HIS compared to LSD (p &lt; 0.05). There was no convincing evidence that INTXSP was greater following HIS than LSD (6.9 ± 3.2 vs 5.8 ± 1.6 mmHg s, p = 0.055). aSBP (126.3 ± 15.4 vs 117.6 ± 10.1 mmHg), aDBP (76.3 ± 6.2 vs 73.1 ± 6.3 mmHg) and aPP (50.0 ± 17.4 vs 44.5 ± 10.8 mmHg) were also higher following HIS compared to LSD (p &lt; 0.05). SVI was similar between HIS and LSD (162.7 ± 29.6 vs 171.6 ± 25.0 %, p = 0.143). A greater aPWV was observed following HIS compared to LSD (5.6 ± 1.6 vs 4.9 ± 0.8 m/s, p = 0.034). Conclusions: Short-term HIS adversely alters reservoir function and central artery haemodynamics in overweight/obese adults. These observations suggest a potential mechanism that may increase cardiovascular disease risk associated with HIS in this population.

ESTIMATION OF DAILY SALT INTAKE IN CHILDREN WITH ESSENTIAL HYPERTENSION

Objective: The development of arterial hypertension is influenced by genetic and environmental factors, with high salt intake being a known environmental contributor. This study aimed to estimate daily salt intake in children with essential arterial hypertension and in normotensive children, and to assess the relationship between their blood pressure values and 24-h urinary sodium excretion. Design and method: Total of 26 children participated in this study; 12 children with essential arterial hypertension (HT) and 14 normotensive children (NT) (both sexes, age ranged 12–17). Systolic, diastolic and mean blood pressure and heart rate were measured. 24-h urine samples were analysed for excreted sodium concentration whereas daily salt intake based on 24-h urinary sodium excretion was calculated using appropriate formula. Statistical analysis was conducted by t-test (between groups), and Pearson’s or Spearman’s correlation test was used to determine the correlations between blood pressure (SBP, DBP and MAP) and 24-h urinary sodium excretion (p &lt; 0.05 was considered statistically significant). Results: Body mass index (BMI) was similar between groups. Calculated salt intake was significantly higher in children with essential hypertension compared with normotensive children. Systolic (SBP), diastolic (DBP) and mean (MAP) arterial blood pressure were significantly higher in children with essential arterial hypertension compared with normotensive children, while there were no difference in heart rate between HT and NT groups. 24-h urinary sodium excretion was significantly higher in the HT compared with the NT group. 24-h urinary sodium excretion was positively associated with SBP (r = 0.673), DBP (r = 0.513) and MAP (r = 0.651). Conclusions: Even though BMI was similar, 24-h urinary sodium excretion was significantly higher in hypertensive children indicating their higher daily salt intake, which is associated with higher blood pressure in these children.

ESTIMATION OF MEAN SALT INTAKE IN LITHUANIA BY 24-HOUR URINARY SODIUM EXCRETION

Objective: High salt intake is associated with increased arterial blood pressure, high risk of other preventable cardiovascular diseases, reduced life expectancy and higher mortality. WHO strongly recommends to take less than 5 g of salt per day. The aim of this study was to evaluate mean salt intake by 24-hour urinary sodium excretion and correlations with arterial blood pressure in Lithuanian population. Design and method: 1034 participants of age 18–69 years were invited to participate in the study and collect 24-hour urine using random sample design. Their blood pressure (BP) was measured 3 times. Arterial hypertension was defined as systolic or diastolic BP &gt; 140/90 mmHg. 146 participants were excluded due to incomplete or inaccurate urine collection and 24 h urinary creatinine excretion outside 2 standard deviations of the sex-specific distribution. Results: 888 participants were included in a final analysis. An average age of participants was 47,4 years and 52,48% were women. Mean calculated salt intake in Lithuania was 10 ± 5,3 g/d. Only 12,5% of subjects consumed WHO recommended salt amount. Results varied between groups: mean salt consumption in males was 11,7 ± 5,8 g/d vs. in females 8,4 ± 4,1 g/d (p &lt; 0,001). 35,1% of participants has hypertension. Female participants had lower mean BP (systolic 119,1 mmHg vs. 129,7 mmHg, diastolic 75,7 mmHg vs. 80,4 mmHg). Sodium excretion and male sex had significant impact on systolic blood pressure in the multiple linear regression model. Conclusions: Salt consumption in Lithuania extremely exceeds recommended amount. Females use less salt and have lower blood pressure.

Traditional Sunchang Gochujang Attenuates Obesity in High-Fat Diet Induced Obese Mice

ObjectivesObesity is a major global health crisis. High fat diet (HFD) and salt intake have been linked to leptin resistance and obesity. Korea has lower obesity prevalence relative to other countries, although Koreans consume various fermented substances containing high salt, such as gochujang and doenjang amongst others. This phenomenon is defined as “the Korean paradox”. Gochujang is a Korean fermented pepper paste that contains high amount of salt. Therefore, we aimed to evaluate the anti-obesity potential of traditional gochujang on HFD-induced obese mice by comparing its effects with HFD and HFD containing same amount of salt from traditional gochujang.Methods4 weeks old C57BL/6J male mice were divided into 4 groups and fed a normal diet (ND), HFD (HD), HFD + salt (SALT) and HFD + traditional sunchang gochujang (TS) diets for 14 weeks. Biochemical analyses of serum, liver, and brown and epididymal fat tissues were performed to assess metabolic changes and obesity-related markers. The expressions of mRNA and protein involved in obesity, lipogenesis, adipogenesis and energy expenditure were evaluated from liver, brown and epididymal fat tissues by qPCR and western blot.ResultsTS supplementation significantly reduced obesity in HFD-induced obese mice. Compared to HD, TS had a lower body weight (24%), reduced serum leptin and insulin levels and improved serum and liver lipid profiles. Compared to HD and SALT groups, TS group had a significant reduction of mRNA and protein expressions associated with anabolic lipid metabolism including leptin, PPARγ, CEBPα, FAS, and ACC, while showing significant increase of adiponectin and energy expenditure-related mRNA, such as PPARα and CPT1.ConclusionsTS ameliorates obesity in HFD-induced obese mice by boosting leptin levels and inhibiting the adipogenesis and lipogenesis. Also, SALT group did not show any improvements compared with TS group. These observations imply that high salt content of TS is not a problematic feature. Our findings prove “the Korean paradox” of gochujang and anti-obesity effects of traditional gochujang, proposing the possibility of the traditional gochujang as a functional food against obesity.Funding SourcesMinistry of Agriculture, Food and Rural Affairs and partly Korea Agro-Fisheries and Food trade corporation.