High sodium (HS) diets can reduce endothelial function (EF) and increase blood pressure (BP) while high potassium (HK) diets are shown to counter this effect. Furthermore, HS diets have also been shown to lead to gut dysbiosis, which is related to increased intestinal permeability (IP). However, the effect of HS diets on IP and whether the addition of HK can attenuate potential HS-induced changes to IP is unknown. Hypotheses: We hypothesized IP would increase on a HS diet and be mitigated by HK and that a higher IP would be related to elevations in BP and lower EF. Methods: Eleven healthy participants (5W/6M, age 32±8 yrs, BMI 23±1, BP 105±6/66±7 mmHg) consumed three 10-day diets of differing sodium and potassium content in randomized order: low sodium (LS)/low potassium (LK) (50mmol/65mmol), HS/LK (300mmol/65mmol), and HS/HK (300mmol/120mmol). On day 9 of each intervention, they collected their urine and wore an ambulatory BP monitor for 24-hr. On day 10, brachial artery flow-mediated dilation (FMD) was measured. Blood was collected and lipopolysaccharide-binding protein (LBP), a biomarker of IP and bacterial translocation, was measured by ELISA. Mixed design ANOVAs assessed sex differences in LBP, FMD, and BPs between diets. Simple linear regressions assessed relations between variables. Results: Twenty-four-hr urinary sodium excretion was higher on both HS diets compared to LS/LK diet (both p<0.01) and 24-hr urinary potassium excretion was higher on HS/HK compared to LS/LK and HS/LK diets (both p<0.01). LBP was different between diets (p<0.01), and there was a significant diet*sex interaction (p=0.02) where men had increased LBP compared to women on the HS/LK and HS/HK diets (both p<0.01). FMD was not different between diets (p=0.13) although men had a lower FMD compared to women after each diet (sex: p<0.01). Twenty-four-hr mean arterial pressure (MAP) was different between diets (p=0.047) as men demonstrated higher 24-hr MAP on the HS/LK diet compared to LS/LK diet (p=0.03) and lower MAP on the HS/HK diet compared to HS/LK diet (p=0.01). LBP was inversely related to FMD (r=-0.82, p<.01) and positively related to MAP (r=0.72, p<.01), 24-hr systolic BP (r=0.66, p=0.03), and 24-hr diastolic BP (r=0.66, p=0.03) on the HS/LK diet for all participants, but not the LS/LK or HS/HK diets. Conclusions: These pilot data suggest that HS diets may increase IP in men, and, in the context of a HS/LK diet, greater IP is associated with lower FMD and higher BP in all participants. NIH R01 HL145055. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiovascular disease (CVD) is influenced by diet quality, such that poor diets generally lead to increased risk. In particular, diets high in sodium have been shown to raise blood pressure (BP) and can lead to arterial stiffening subsequently increasing CVD risk. Current sodium recommendations aimed at lowering CVD risk are given in absolute amounts and do not account for total energy intake. This makes it difficult for individuals with greater energy intakes to meet daily recommended targets. Dietary sodium density (i.e., mg sodium/kcal energy) has been suggested to be a stronger determinant of BP than absolute sodium intake; however, the relation between sodium density and vascular health has yet to be studied in normotensive adults. Our objective was to examine the association between sodium density and ambulatory BP and arterial stiffness in young, healthy, normotensive adults. We hypothesized that sodium density would relate to 24-hour BP and arterial stiffness just as absolute sodium intake does. Sixty-two participants (23M/39W, age 27±6 years, BMI 23.4±2.7 kg/m², BP 112±11/69±9 mmHg) recorded their habitual diet for three days and wore an ambulatory BP monitor to assess 24-hour, daytime, and nighttime BP. Arterial stiffness was assessed by pulse wave velocity (PWV) and wave reflection with augmentation index (AIx). Associations between absolute sodium intake and sodium density with BP and stiffness measures were assessed using bivariate and partial Pearson correlations. On average, participants consumed 2029±547 kcals and 3250±1231 mg sodium. Daytime BP was 118±11/70±7 mmHg and nighttime BP was 106±14/58±9 mmHg. Sodium intake (r=0.31, p=0.03) and sodium density (r=0.35, p=0.01) both correlated with nighttime systolic BP but not nighttime diastolic BP nor daytime or 24-hour systolic or diastolic BP. After controlling for age and sex, both sodium intake (r=0.44, p=0.01) and sodium density (r=0.56, p<0.001) remained significantly associated with nighttime systolic BP. There were no significant correlations between sodium intake or sodium density and PWV or AIx (all p>0.05). These findings indicate sodium density is associated with elevated BP, specifically nighttime systolic BP, in healthy young men and women, suggesting sodium density relates to BP as strongly as absolute sodium intake. Supported by NIH Grant 1R01HL145055 and P20GM113125. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

High sodium diets (HSD) have been shown to both increase blood pressure (BP) and lead to gut dysbiosis in adults. Gut dysbiosis can increase intestinal permeability (IP), allowing for translocation of bacteria and their products into the systemic circulation. There, bacteria and their products are recognized by the immune system and can activate pro-inflammatory pathways such as TH17 in a dose dependent manner. HSD has been shown to activate those pathways and increase BP in men. However, the effect of a HSD on IP has not been explored as a potential mechanism of HSD induced BP changes. The objective of this research was to investigate if a HSD can increase IP and inflammatory markers. We hypothesized that plasma concentrations of two common biomarkers of IP, zonulin and LPS binding protein (LBP), and proinflammatory TH17 lymphocytes would increase, while anti-inflammatory Treg lymphocytes would decrease on a HSD compared to a recommended sodium diet (RSD). Twenty-seven healthy participants (15W/12M, age 24±3 yrs, BP 112±9/65±6 mmHg) underwent a 10-day HSD (6,900mg sodium/d, supplemented by salt pills) and a 10-day RSD (2,300 mg sodium/d) intervention in randomized order. On day 9 of each intervention, participants collected urine and wore an ambulatory BP monitor for 24hr. Blood was collected to measure plasma zonulin and LBP by ELISA. TH17 and Treg populations were characterized from PBMCs by flow cytometry. Paired t-tests were used to compare variables on day 9 between diets. Pearson correlations were used to assess the relation between markers of IP and BP. Twenty-four-hour sodium excretion was increased on the HSD (RSD: 135±57 mmol/24h, HSD: 290±68 mmol/24h, p<0.0001). Mean 24-hr SBP (RSD: 116±10, HSD: 117±11 p=0.70) and DBP (RSD: 66±6 mmHg, HSD: 66±5 mmHg, p=0.84) were not different between diets. Plasma zonulin concentrations (RSD: 2.6±1.6 ng/ml, HSD: 2.6±1.5 ng/ml p=0.88) and LBP concentrations (RSD: 3.2±1.7 μg/ml, HSD: 3.2±1.8 μg/ml, p=0.72) were not different between diets. The TH17/Treg ratio was not different between diets (RSD: 0.54±0.51, HSD: 0.41±0.38; p=0.21) however the ratio was inversely associated with zonulin (r=-0.57 p=0.04), and LBP (r=-0.61; p=0.012) on HSD when controlling for age and sex but not on RSD (all p>0.05). These data suggest that 10 days of a HSD did not change IP, BP or T lymphocyte populations in young, healthy individuals. However, the TH17/Treg ratio was associated with zonulin and LBP suggesting that the immune system may respond to changes in IP. Future research is needed to determine whether a HSD can affect IP and inflammation in salt sensitive populations. NIH Grants R01 HL145055 and P20GM113125 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Mild metabolic acidosis, as influenced by dietary intake, has been the topic of many epidemiological studies as a contributing factor to developing high blood pressure (BP). Diets that include an abundance of fruits and vegetables are marked by a high potassium intake that contributes to a decreased renal acid load. In contrast, a Western diet, which is typically deficient in potassium and higher in protein and phosphorus, is characterized by a higher acid load that may negatively alter acid-base balance and contribute to future cardiovascular events. The purpose of this study was to investigate the relation between dietary acid load and BP in healthy adults. Healthy adults aged 18-79 years old were included in this retrospective analysis. Dietary acid load was approximated using the Potential Renal Acid Load (PRAL), which is strongly influenced by dietary intake of protein, phosphorus and potassium assessed from a 3-day diet record. The average of three seated BP measurements was used for our analysis. Associations between PRAL and BP were determined using bivariate and partial Pearson correlations. One hundred and fifty-four subjects (78M/76W; 39 ± 2 yrs; BMI 25 ± 0.3 kg/m²) were included in this study. Men had a higher BMI (26 ± 1 kg/m² vs. 25 ± 1 kg/m²; p=0.03) and BP (119 ± 1/70 ± 1 vs. 111 ± 2/67 ± 1 mmHg; p<0.05) than women. Average PRAL was 13.4 ± 1.6 mEq/day and is consistent with a high protein and low potassium diet. PRAL values were also greater in men than women (18.6 ± 2.6 mEq/day vs. 8.1 ± 1.8 mEq/day; p<0.05). Total energy intake was 2089 ± 48 kcals/day, with men consuming more energy than women (2340 ± 70 kcals/day vs. 1835 ± 51 kcals/day; p<0.001). PRAL was positively associated with systolic BP (SBP) and pulse pressure (PP) (SBP: r=0.171, p=0.034; PP: r=0.261, p=0.001) but not with diastolic BP (DBP: r=-0.050, p=0.539). When sex and age were included as covariates, PRAL was positively correlated with both SBP and PP (SBP: r=0.205, p=0.011; PP: r=0.234, p=0.004) but not DBP (DBP: r=0.007, p=0.936). In conclusion, these findings indicate that a higher dietary acid load, correlates with a higher SBP and PP. This relation remains even after accounting for age and sex.