Mechanisms of Dietary Sodium-Induced Impairments in Endothelial Function and Potential Countermeasures

Despite decades of efforts to reduce sodium intake, excess dietary sodium remains commonplace, and contributes to increased cardiovascular morbidity and mortality independent of its effects on blood pressure. An increasing amount of research suggests that high-sodium diets lead to reduced nitric oxide-mediated endothelial function, even in the absence of a change in blood pressure. As endothelial dysfunction is an early step in the progression of cardiovascular diseases, the endothelium presents a target for interventions aimed at reducing the impact of excess dietary sodium. In this review, we briefly define endothelial function and present the literature demonstrating that excess dietary sodium results in impaired endothelial function. We then discuss the mechanisms through which sodium impairs the endothelium, including increased reactive oxygen species, decreased intrinsic antioxidant defenses, endothelial cell stiffening, and damage to the endothelial glycocalyx. Finally, we present selected research findings suggesting that aerobic exercise or increased intake of dietary potassium may counteract the deleterious vascular effects of a high-sodium diet.

Download Full-text

Abstract P106: Effects of Aldosterone Excess and Sodium on Dipping Patterns in Resistant Hypertensive Patients

Hypertension ◽

10.1161/hyp.68.suppl_1.p106 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Charles German

Keyword(s):

Blood Pressure ◽

Ambulatory Blood Pressure ◽

Sodium Excretion ◽

Sodium Intake ◽

Large Body ◽

Dietary Sodium ◽

Hypertensive Patients ◽

Nocturnal Hypertension ◽

High Sodium ◽

Cardiovascular Morbidity And Mortality

Background: High dietary sodium intake and aldosterone excess have been independently linked to increased cardiovascular morbidity and mortality. In addition, a large body of literature indicates that aldosterone excess contributes importantly to antihypertensive treatment resistance and is associated with higher 24- hour ambulatory blood pressure (BP) levels. Objective: This study was designed to determine if high dietary sodium intake, and hyperaldosteronism combine to mediate the development of abnormal diurnal BP patterns including nocturnal hypertension and dipping BP patterns. Methods: A single-center cohort of 326 African American (AA) and Caucasian resistant hypertensive patients were prospectively evaluated by assessing 24-hr urinary aldosterone (UAldo), plasma renin activity (PRA), sodium (UNa + ) levels, and 24-hr ambulatory blood pressure monitoring (ABPM). Daytime, night-time, and 24-hr BP and dipping patterns were determined. High sodium excretion was defined as UNa + = 200 mEq/24hr and hyperaldosteronism was defined as UAldo = 12 μg/24hr and PRA ≤ 1 ng/ml/hr. Results: There was no difference in ABPM and dipping patterns when comparing the normal versus high sodium group. However, patients without high sodium excretion had better nocturnal (p=0.024) and 24- hour BP control (p=0.036). Furthermore, there was no difference in ABPM patterns when comparing patients with high versus normal sodium excretion with hyper versus non- hyperaldosteronism. Interestingly, in the group with hyperaldosteronism, patients with normal sodium excretion had improved dipping patterns, but only in the dipper group (p=0.016). Conclusions: High dietary sodium intake contributes to increased nocturnal hypertension and poor 24-h BP control, but there does not seem to be a significant relationship between hyperaldosteronism and high dietary sodium intake. This data suggests that improvements in dietary sodium intake will lead to better control of nighttime BP and 24-h BP control and therefore reduces the risk of cardiovascular disease. Further studies are underway comparing these relationships in males versus females, and AAs versus Caucasians.

Download Full-text

Abstract P276: A High Sodium Diet Reduces Cutaneous Microvascular Function In Normotensive Individuals With Salt Sensitive Blood Pressure

Hypertension ◽

10.1161/hyp.78.suppl_1.p276 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Jordan C Patik ◽

Joseph M Stock ◽

Nathan T Romberger ◽

Shannon L Lennon ◽

William B Farquhar ◽

...

Keyword(s):

Blood Pressure ◽

Vascular Function ◽

Sodium Intake ◽

Local Heating ◽

Urinary Sodium Excretion ◽

Microvascular Function ◽

Dietary Sodium ◽

Heating Unit ◽

Doppler Flowmetry ◽

High Sodium

Impaired vascular function likely contributes to the association between dietary sodium intake and the development of cardiovascular disease. Using the cutaneous microvasculature as a model, we have previously shown that a high sodium (HS) diet blunts local heating-induced vasodilation in normotensive individuals with salt resistant (SR) blood pressure (BP). However, the effect of a HS diet on the cutaneous microvasculature in normotensive salt sensitive (SS) individuals remains unclear. Therefore, we tested the hypothesis that cutaneous microvascular function is reduced by a HS diet to a greater degree in SS compared to SR individuals. After each 7-day controlled feeding diet (low sodium (LS) = 20 mmol/day; HS = 300 mmol/day), an intradermal microdialysis fiber was inserted in the ventral forearm and perfused with Ringer’s solution. Skin blood flow (SkBF) was continuously monitored via laser Doppler flowmetry and a local heating unit was placed over the fiber and heated to 42°C until SkBF reached a stable plateau. Site-specific maximal SkBF was determined by perfusing 28mM sodium nitroprusside and heating to 43°C. Mean arterial pressure (MAP) was assessed at regular intervals on the contralateral arm and was used to calculate cutaneous vascular conductance (CVC = SkBF / MAP). Subjects wore a 24-hr ambulatory BP monitor and collected their urine on the final day of each diet. Fourteen subjects (9W / 5M, 42 ± 14 yr) whose MAP increased >5 mmHg (Δ8 ± 1 mmHg) on the HS diet were defined as SS and were compared to 14 age- (43± 14 yr) and sex-matched SR subjects (Δ1 ± 3 mmHg). SS and SR had similar MAP at baseline (88 ± 9 vs. 90 ± 8 mmHg, P = 0.88) and urinary sodium excretion was increased similarly across groups by the HS diet (Δ239 ± 104 vs. Δ220 ± 66 mmol / 24 hr, P = 0.20). Cutaneous vasodilation in response to local heating was decreased on the HS diet relative to the LS diet in both SS (Δ-9 ± 9 %CVCmax, P = 0.005) and SR (Δ-9 ± 9 %CVCmax, P=0.005); however, there was not a group x diet interaction (P = 0.99). In contrast to our hypothesis, these results suggest that the deleterious effects of high sodium diets on cutaneous microvascular function are similar in normotensive salt sensitive and salt resistant individuals.

Download Full-text

Sodium Intake and Hypertension

Nutrients ◽

10.3390/nu11091970 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1970 ◽

Cited By ~ 28

Author(s):

Grillo ◽

Salvi ◽

Coruzzi ◽

Salvi ◽

Parati

Keyword(s):

Blood Pressure ◽

Salt Intake ◽

Sodium Intake ◽

Peripheral Resistance ◽

Dietary Sodium ◽

Dietary Salt ◽

High Sodium ◽

Close Relationship ◽

And Function ◽

Modest Reduction

The close relationship between hypertension and dietary sodium intake is widely recognized and supported by several studies. A reduction in dietary sodium not only decreases the blood pressure and the incidence of hypertension, but is also associated with a reduction in morbidity and mortality from cardiovascular diseases. Prolonged modest reduction in salt intake induces a relevant fall in blood pressure in both hypertensive and normotensive individuals, irrespective of sex and ethnic group, with larger falls in systolic blood pressure for larger reductions in dietary salt. The high sodium intake and the increase in blood pressure levels are related to water retention, increase in systemic peripheral resistance, alterations in the endothelial function, changes in the structure and function of large elastic arteries, modification in sympathetic activity, and in the autonomic neuronal modulation of the cardiovascular system. In this review, we have focused on the effects of sodium intake on vascular hemodynamics and their implication in the pathogenesis of hypertension.

Download Full-text

High-sodium intake prevents pregnancy-induced decrease of blood pressure in the rat

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01132.2002 ◽

2003 ◽

Vol 285 (1) ◽

pp. H375-H383 ◽

Cited By ~ 35

Author(s):

Annie Beauséjour ◽

Karine Auger ◽

Jean St-Louis ◽

Michèle Brochu

Keyword(s):

Blood Pressure ◽

Systolic Blood Pressure ◽

Sodium Intake ◽

Plasma Sodium ◽

Mrna Levels ◽

Sprague Dawley ◽

Pregnant Rats ◽

High Sodium ◽

High Sodium Intake ◽

The Impact

Despite an increase of circulatory volume and of renin-angiotensin-aldosterone system (RAAS) activity, pregnancy is paradoxically accompanied by a decrease in blood pressure. We have reported that the decrease in blood pressure was maintained in pregnant rats despite overactivation of RAAS following reduction in sodium intake. The purpose of this study was to evaluate the impact of the opposite condition, e.g., decreased activation of RAAS during pregnancy in the rat. To do so, 0.9% or 1.8% NaCl in drinking water was given to nonpregnant and pregnant Sprague-Dawley rats for 7 days (last week of gestation). Increased sodium intakes (between 10- and 20-fold) produced reduction of plasma renin activity and aldosterone in both nonpregnant and pregnant rats. Systolic blood pressure was not affected in nonpregnant rats. However, in pregnant rats, 0.9% sodium supplement prevented the decreased blood pressure. Moreover, an increase of systolic blood pressure was obtained in pregnant rats receiving 1.8% NaCl. The 0.9% sodium supplement did not affect plasma and fetal parameters. However, 1.8% NaCl supplement has larger effects during gestation as shown by increased plasma sodium concentration, hematocrit level, negative water balance, proteinuria, and intrauterine growth restriction. With both sodium supplements, decreased AT1 mRNA levels in the kidney and in the placenta were observed. Our results showed that a high-sodium intake prevents the pregnancy-induced decrease of blood pressure in rats. Nonpregnant rats were able to maintain homeostasis but not the pregnant ones in response to sodium load. Furthermore, pregnant rats on a high-sodium intake (1.8% NaCl) showed some physiological responses that resemble manifestations observed in preeclampsia.

Download Full-text

Dietary Sodium Restriction in the Management of Chronic Kidney Disease: A Systematic Review and Meta-Analysis of RCTs

10.21203/rs.3.rs-806377/v1 ◽

2021 ◽

Author(s):

Sai Sidharth Manikandan ◽

Murali Dhar

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Salt Intake ◽

Sodium Intake ◽

Meta Analysis ◽

Cost Effective ◽

Mean Difference ◽

Dietary Sodium ◽

High Sodium

Abstract Background: Non-pharmacological strategies such as lowering sodium intake aim to protect renal function and delay the initiation of renal replacement therapy. It might also be a cost-effective method to improve chronic kidney disease (CKD) prognosis. We decided to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of low versus high sodium intake in adults with CKD. Results:Our search strategy yielded seven studies from six countries with 465 participants. The overall effect on restricted sodium intake favored reduction in systolic blood pressure with an overall mean difference of -6.14(95% CI: -9.52, -2.76) and reduction in diastolic blood pressure with a mean difference of -3.08 (95% CI: -4.62, -1.55). There was lowering of estimated glomerular filtration rate (eGFR), however the same was not statistically significant.Conclusion:The study found that restricted salt intake could significantly reduce systolic and diastolic BP. Further, multi-center RCTs for longer durations across different stages of CKD could effectively assess the effects of restricted sodium intake on vital parameters. Such study designs could also help clinicians identify the optimal intake of dietary sodium to achieve better renal and cardio vascular outcomes.

Download Full-text

Dietary sodium and central vs. peripheral ouabain-like activity in Dahl salt-sensitive vs. salt-resistant rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.5.h1916 ◽

1994 ◽

Vol 267 (5) ◽

pp. H1916-H1920 ◽

Cited By ~ 14

Author(s):

F. H. Leenen ◽

E. Harmsen ◽

H. Yu

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Sodium Intake ◽

Dietary Sodium ◽

High Sodium ◽

High Sodium Intake ◽

Pressor Responses ◽

Excess Sodium

To assess the possible contribution of brain ouabain-like activity (OLA) to the pressor effects of high-sodium intake in Dahl salt-sensitive (Dahl S) rats, we assessed the effects of high (8%) on blood pressure (BP) and peripheral and brain OLA in Dahl on blood pressure (BP) and peripheral and brain OLA in Dahl S and Dahl salt-resistant (Dahl R) rats. On regular sodium intake, Dahl S and R had similar BP; however, by 7 wk of age adrenal and plasma OLA were 15–30% higher in Dahl S vs. R, whereas central OLA remained similar. On high-sodium intake, in Dahl S both peripheral and central OLA increased within 1 wk with additional increases after 3 wk. These increases preceded the rise in BP. In Dahl R rats, high sodium did not increase BP. However, 3 wk of high sodium did increase peripheral as well as central OLA, the latter to a lesser extent compared with Dahl S and not in the hypothalamus. These results are consistent with the concept that central OLA may be involved in the pressor responses to high sodium in Dahl S. Circulating OLA may play a role in the regulation of renal function to excrete excess sodium in both strains.

Download Full-text

The Impact of High Dietary Sodium Consumption on Blood Pressure Variability in Healthy, Young Adults

American Journal of Hypertension ◽

10.1093/ajh/hpaa014 ◽

2020 ◽

Vol 33 (5) ◽

pp. 422-429 ◽

Cited By ~ 2

Author(s):

Kamila U Migdal ◽

Matthew C Babcock ◽

Austin T Robinson ◽

Joseph C Watso ◽

Megan M Wenner ◽

...

Keyword(s):

Blood Pressure ◽

Blood Pressure Variability ◽

Salt Intake ◽

Secondary Analysis ◽

Organ Damage ◽

Healthy Adults ◽

Dietary Sodium ◽

High Sodium ◽

Ambulatory Bp Monitoring ◽

The Impact

Abstract BACKGROUND High sodium (Na+) intake augments blood pressure variability (BPV) in normotensive rodents, without changes in resting blood pressure (BP). Augmented BPV is associated with end-organ damage and cardiovascular morbidity. It is unknown if changes in dietary Na+ influence BPV in humans. We tested the hypothesis that high Na+ feeding would augment BPV in healthy adults. METHODS Twenty-one participants (10 F/11 M; 26 ± 5 years; BP: 113 ± 11/62 ± 7 mm Hg) underwent a randomized, controlled feeding study that consisted of 10 days of low (2.6 g/day), medium (6.0 g/day), and high (18.0 g/day) salt diets. On the ninth day of each diet, 24-h urine samples were collected and BPV was calculated from 24-h ambulatory BP monitoring. On the tenth day, in-laboratory beat-to-beat BPV was calculated during 10 min of rest. Serum electrolytes were assessed. We calculated average real variability (ARV) and standard deviation (SD) as metrics of BPV. As a secondary analysis, we calculated central BPV from the 24-h ambulatory BP monitoring. RESULTS 24-h urinary Na+ excretion (low = 41 ± 24, medium = 97 ± 43, high = 265 ± 92 mmol/24 h, P < 0.01) and serum Na+ (low = 140.0 ± 2.1, medium = 140.7 ± 2.7, high = 141.7 ± 2.5 mmol/l, P = 0.009) increased with greater salt intake. 24-h ambulatory ARV (systolic BP ARV: low = 9.5 ± 1.7, medium = 9.5 ± 1.2, high = 10.0 ± 1.9 mm Hg, P = 0.37) and beat-to-beat ARV (systolic BP ARV: low = 2.1 ± 0.6, medium = 2.0 ± 0.4, high = 2.2 ± 0.8 mm Hg, P = 0.46) were not different. 24-h ambulatory SD (systolic BP: P = 0.29) and beat-to-beat SD (systolic BP: P = 0.47) were not different. There was a trend for a main effect of the diet (P = 0.08) for 24-h ambulatory central systolic BPV. CONCLUSIONS Ten days of high sodium feeding does not augment peripheral BPV in healthy, adults. CLINICAL TRIALS REGISTRATION NCT02881515.

Download Full-text

Dietary Na and baroreflex modulation of blood pressure and RSNA in normotensive vs. spontaneously hypertensive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.266.2.h496 ◽

1994 ◽

Vol 266 (2) ◽

pp. H496-H502 ◽

Cited By ~ 13

Author(s):

B. S. Huang ◽

F. H. Leenen

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Sodium Intake ◽

Marked Change ◽

Dietary Sodium ◽

Hypertensive Rats ◽

Baroreflex Control ◽

Spontaneously Hypertensive ◽

High Sodium ◽

Wistar Kyoto

Different changes in baroreflex control of the circulation have been postulated to play a role in the different blood pressure (BP) effects of dietary sodium in normotensive vs. genetically hypertensive rats. We therefore evaluated in young Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), with or without chronic sinoaortic denervation (SAD), the effects of low, regular, and high dietary sodium intake from 4 to 8 wk of age on BP and baroreflex function. The latter was assessed by changes in renal sympathetic nerve activity (RSNA) and heart rate in response to (de)pressor agents. In SHR, the above range of sodium caused a marked change in resting BP, somewhat more in intact (48 mmHg) vs. SAD (36 mmHg) rats. In contrast, in WKY this range of sodium intake caused only a minor (7 mmHg) change in resting BP of intact WKY but a significant (16 mmHg) change in WKY with SAD, mainly due to an increase in BP on high sodium. In intact WKY increasing dietary sodium from low to regular to high caused stepwise increases in the gain of the RSNA-BP reflex, whereas in intact SHR only an increase from low to regular sodium intake increased the gain. After SAD, the gain of the RSNA-BP reflex was very low, and no longer affected by dietary sodium in either strain. These data suggest that in WKY a sensitization in arterial baroreflex control of RSNA prevents a sodium-induced increase in BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Abstract P333: The Impact of Sodium on Blood Pressure and Arterial Stiffness is Moderated by Indices of Obesity in People of African Ancestry.

Hypertension ◽

10.1161/hyp.68.suppl_1.p333 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Maseko Muzi

Keyword(s):

Blood Pressure ◽

Waist Circumference ◽

Arterial Stiffness ◽

Sodium Intake ◽

African Ancestry ◽

Applanation Tonometry ◽

Dietary Sodium ◽

High Incidence ◽

The Impact ◽

The Relationship

Background: Obesity is on the rise worldwide and like Na + it is associated with blood pressure (BP) and target organ changes. Our study population has a high incidence of obesity (67%) and a dietary sodium intake that is slightly above the recommended threshold. Previous studies conducted in this population have shown no relationship between Na + and both BP and arterial stiffness. With the high incidence of obesity in this population, it is possible that the indices of obesity blunt this relationship. Therefore in this study we investigate whether the relationship between Na + and both BP and PWV is moderated by the indices of obesity. Methods: We recruited 1219 South Africans of African ancestry and measure 24-h ambulatory on 796 participants and 597 had complete 24-hour urine collection. Anthropometric measurements were taken and a standard questionnaire was issued to determine lifestyle habits and history of medication. To assess arterial stiffness we used applanation tonometry to measure pulse wave velocity (PWV). Results: After correcting for covariates, there was an association between Na + and PB in participants with normal BMI but not in obese participants. Similarly there was a relationship between Na + and PWV (p=0.0447) in individuals with normal BMI only. When waist circumference was used as an index of obesity, gender disparities were observed in the relationship between Na + and PWV. There was no relationship between Na + and PWV irrespective the waist circumference in males but a multivariate regression analyses showed a relationship between Na + and PWV in all women (p=0.0142) and in women with a normal waist circumference (p=0.0006). Conclusion: In a population with a high incidence of obesity, the relationship between Na + and both BP and PWV is modified by the indices of obesity.

Download Full-text