scholarly journals Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

2008 ◽  
Vol 294 (3) ◽  
pp. H1258-H1265 ◽  
Author(s):  
Luminita H. Pojoga ◽  
Tham M. Yao ◽  
Sumi Sinha ◽  
Reagan L. Ross ◽  
Jeffery C. Lin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Vascular Function ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Vascular Relaxation ◽  
Enos Expression ◽  
Vascular Contraction ◽  
Caveolin 1 ◽  
Enos Activity

Changes in dietary sodium intake are associated with changes in vascular volume and reactivity that may be mediated, in part, by alterations in endothelial nitric oxide synthase (eNOS) activity. Caveolin-1 (Cav-1), a transmembrane anchoring protein in the plasma membrane caveolae, binds eNOS and limits its translocation and activation. To test the hypothesis that endothelial Cav-1 participates in the dietary sodium-mediated effects on vascular function, we assessed vascular responses and nitric oxide (NO)-mediated mechanisms of vascular relaxation in Cav-1 knockout mice (Cav-1−/−) and wild-type control mice (WT; Cav-1+/+) placed on a high-salt (HS; 4% NaCl) or low-salt (LS; 0.08% NaCl) diet for 16 days. After the systolic blood pressure was measured, the thoracic aorta was isolated for measurement of vascular reactivity and NO production, and the heart was used for measurement of eNOS expression and/or activity. The blood pressure was elevated in HS mice treated with NG-nitro-l-arginine methyl ester and more so in Cav-1−/− than WT mice and was significantly reduced during the LS diet. Phenylephrine caused vascular contraction that was significantly reduced in Cav-1−/− (maximum 0.25 ± 0.06 g/mg) compared with WT (0.75 ± 0.22 g/mg) on the HS diet, and the differences were eliminated with the LS diet. Also, vascular contraction in response to membrane depolarization by high KCl (96 mM) was reduced in Cav-1−/− (0.27 ± 0.05 g/mg) compared with WT mice (0.53 ± 0.12 g/mg) on the HS diet, suggesting that the reduced vascular contraction is not limited to a particular receptor. Acetylcholine (10−5 M) caused aortic relaxation in WT mice on HS (23.6 ± 3.5%) and LS (23.7 ± 5.5%) that was enhanced in Cav-1−/− HS (72.6 ± 6.1%) and more so in Cav-1−/− LS mice (93.6 ± 3.5%). RT-PCR analysis indicated increased eNOS mRNA expression in the aorta and heart, and Western blots indicated increased total eNOS and phosphorylated eNOS in the heart of Cav-1−/− compared with WT mice on the HS diet, and the genotypic differences were less apparent during the LS diet. Thus Cav-1 deficiency during the HS diet is associated with decreased vasoconstriction, increased vascular relaxation, and increased eNOS expression and activity, and these effects are altered during the LS diet. The data support the hypothesis that endothelial Cav-1, likely through an effect on eNOS activity, plays a prominent role in the regulation of vascular function during substantial changes in dietary sodium intake.

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

Hypertension ◽  
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.

scholarly journals Sensitivity of NOS-dependent vascular relaxation pathway to mineralocorticoid receptor blockade in caveolin-1-deficient mice

2010 ◽  
Vol 298 (6) ◽  
pp. H1776-H1788 ◽  
Author(s):  
Luminita H. Pojoga ◽  
Zuzana Adamová ◽  
Abhinav Kumar ◽  
Amanda K. Stennett ◽  
Jose R. Romero ◽  
...  
Keyword(s):  
Vascular Function ◽  
Mineralocorticoid Receptor ◽  
Vascular Reactivity ◽  
Steroid Receptors ◽  
Inhibitory Effect ◽  
Vascular Relaxation ◽  
Enos Expression ◽  
Western Blots ◽  
Caveolin 1 ◽  
Deficient Mice

Endothelial caveolin-1 (cav-1) is an anchoring protein in plasma membrane caveolae where it binds endothelial nitric oxide synthase (eNOS) and limits its activation, particularly in animals fed a high salt (HS) diet. Cav-1 also interacts with steroid receptors such as the mineralocorticoid receptor (MR). To test the hypothesis that vascular reactivity is influenced by an interplay between MR and cav-1 during HS diet, we examined the effects of MR blockade on NOS-mediated vascular relaxation in normal and cav-1-deficient mice. Wild-type (WT) and cav-1 knockout mice (cav-1−/−) were fed for 14 days a HS (4% NaCl) diet with and without the MR antagonist eplerenone (Epl; 100 mg·kg−1·day−1). After systolic blood pressure (BP) was measured, the thoracic aorta was isolated for measurement of vascular reactivity, and the aorta and heart were used for measurement of eNOS and MR expression. BP was not different between WT + Epl and WT, but was higher in cav-1−/− + Epl than in cav-1−/− mice. Phenylephrine (Phe)-induced vascular contraction was less in cav-1−/− than WT, and significantly enhanced in cav-1−/− + Epl than in cav-1−/−, but not in WT + Epl compared with WT. Endothelium removal and NOS blockade by Nω-nitro-l-arginine methyl ester (l-NAME) enhanced Phe contraction in cav-1−/−, but not cav-1−/− + Epl. ACh-induced aortic relaxation was reduced in cav-1−/− + Epl versus cav-1−/−, but not in WT + Epl compared with WT. Endothelium removal, l-NAME, and the guanylate cyclase inhibitor ODQ abolished the large ACh-induced relaxation in cav-1−/− and the remaining relaxation in the cav-1−/− + Epl but had similar inhibitory effect in WT and WT + Epl. Real-time RT-PCR indicated decreased eNOS mRNA expression in the aorta and heart, and Western blots revealed decreased total eNOS in the heart of cav-1−/− + Epl compared with cav-1−/−. Vascular and cardiac MR expression was less in cav-1−/− than WT, but not in cav-1−/− + Epl compared with cav-1−/−. Plasma aldosterone (Aldo) was not different between WT and cav-1−/− mice nontreated or treated with Epl. Thus in cav-1 deficiency states and HS diet MR blockade is associated with increased BP, enhanced vasoconstriction, and decreased NOS-mediated vascular relaxation and eNOS expression. The data suggest that, in the absence of cav-1, MR activation plays a beneficial role in regulating eNOS expression/activity and, consequently, the vascular function during HS diet.

scholarly journals The Effects of Short-Term Changes in Sodium Intake on Plasma Marinobufagenin Levels in Patients with Primary Salt-Sensitive and Salt-Insensitive Hypertension

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1502
Author(s):  
Katarzyna Łabno-Kirszniok ◽  
Agata Kujawa-Szewieczek ◽  
Andrzej Wiecek ◽  
Grzegorz Piecha
Keyword(s):  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Sodium Intake ◽  
Left Ventricular ◽  
Primary Hypertension ◽  
Dietary Sodium ◽  
Sodium Restriction ◽  
Short Term ◽  
Salt Loading ◽  
Dietary Sodium Restriction

Increased marinobufagenin (MBG) synthesis has been suggested in response to high dietary salt intake. The aim of this study was to determine the effects of short-term changes in sodium intake on plasma MBG levels in patients with primary salt-sensitive and salt-insensitive hypertension. In total, 51 patients with primary hypertension were evaluated during acute sodium restriction and sodium loading. Plasma or serum concentrations of MBG, natriuretic pro-peptides, aldosterone, sodium, potassium, as well as hematocrit (Hct) value, plasma renin activity (PRA) and urinary sodium and potassium excretion were measured. Ambulatory blood pressure monitoring (ABPM) and echocardiography were performed at baseline. In salt-sensitive patients with primary hypertension plasma MBG correlated positively with diastolic blood pressure (ABPM) and serum NT-proANP concentration at baseline and with serum NT-proANP concentration after dietary sodium restriction. In this subgroup plasma MBG concentration decreased during sodium restriction, and a parallel increase of PRA was observed. Acute salt loading further decreased plasma MBG concentration in salt-sensitive subjects in contrast to salt insensitive patients. No correlation was found between plasma MBG concentration and left ventricular mass index. In conclusion, in salt-sensitive hypertensive patients plasma MBG concentration correlates with 24-h diastolic blood pressure and dietary sodium restriction reduces plasma MBG levels. Decreased MBG secretion in response to acute salt loading may play an important role in the pathogenesis of salt sensitivity.

Renal and cardiac oxidative/nitrosative stress in salt-loaded pregnant rat

2007 ◽  
Vol 293 (4) ◽  
pp. R1657-R1665 ◽  
Author(s):  
Annie Beauséjour ◽  
Véronique Houde ◽  
Karine Bibeau ◽  
Rébecca Gaudet ◽  
Jean St-Louis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitrosative Stress ◽  
Gestational Hypertension ◽  
Sodium Intake ◽  
Pregnant Rats ◽  
High Sodium ◽  
High Sodium Intake ◽  
Arterial Blood ◽  
Cardiac Ventricle

Sodium supplementation given for 1 wk to nonpregnant rats induces changes that are adequate to maintain renal and circulatory homeostasis as well as arterial blood pressure. However, in pregnant rats, proteinuria, fetal growth restriction, and placental oxidative stress are observed. Moreover, the decrease in blood pressure and expansion of circulatory volume, normally associated with pregnancy, are prevented by high-sodium intake. We hypothesized that, in these pregnant rats, a loss of the balance between prooxidation and antioxidation, particularly in kidneys and heart, disturbs the normal course of pregnancy and leads to manifestations such as gestational hypertension. We thus investigated the presence of oxidative/nitrosative stress in heart and kidneys following high-sodium intake in pregnant rats. Markers of this stress [8-isoprostaglandin F2α (8-iso-PGF2α) and nitrotyrosine], producer of nitric oxide [nitric oxide synthases (NOSs)], and antioxidants [superoxide dismutase (SOD) and catalase] were measured. Then, molecules (Na+-K+-ATPase and aconitase) or process [apoptosis (Bax and Bcl-2), inflammation (monocyte chemoattractant protein-1, connective tissue growth factor, and TNF-α)] susceptible to free radicals was determined. In kidneys from pregnant rats on 1.8% NaCl-water, NOSs, apoptotic index, and nitrotyrosine expression were increased, whereas Na+-K+-ATPase mRNA and activity were decreased. In the left cardiac ventricle of these rats, heightened nitrotyrosine, 8-iso-PGF2α, and catalase activity together with reduced endothelial NOS protein expression and SOD and aconitase activities were observed. These findings suggest that oxidative/nitrosative stress in kidney and left cardiac ventricle destabilizes the normal course of pregnancy and could lead to gestational hypertension.

scholarly journals Blood Pressure Effects of Sodium Reduction

Circulation ◽  
2021 ◽  
Vol 143 (16) ◽  
pp. 1542-1567 ◽  
Author(s):  
Tommaso Filippini ◽  
Marcella Malavolti ◽  
Paul K. Whelton ◽  
Androniki Naska ◽  
Nicola Orsini ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Clinical Trials ◽  
Linear Relationship ◽  
Dose Response ◽  
Sodium Intake ◽  
Experimental Studies ◽  
Dietary Sodium ◽  
Response Analysis ◽  
Sodium Reduction

Background: The relationship between dietary sodium intake and blood pressure (BP) has been tested in clinical trials and nonexperimental human studies, indicating a direct association. The exact shape of the dose–response relationship has been difficult to assess in clinical trials because of the lack of random-effects dose–response statistical models that can include 2-arm comparisons. Methods: After performing a comprehensive literature search for experimental studies that investigated the BP effects of changes in dietary sodium intake, we conducted a dose–response meta-analysis using the new 1-stage cubic spline mixed-effects model. We included trials with at least 4 weeks of follow-up; 24-hour urinary sodium excretion measurements; sodium manipulation through dietary change or supplementation, or both; and measurements of systolic and diastolic BP at the beginning and end of treatment. Results: We identified 85 eligible trials with sodium intake ranging from 0.4 to 7.6 g/d and follow-up from 4 weeks to 36 months. The trials were conducted in participants with hypertension (n=65), without hypertension (n=11), or a combination (n=9). Overall, the pooled data were compatible with an approximately linear relationship between achieved sodium intake and mean systolic as well as diastolic BP, with no indication of a flattening of the curve at either the lowest or highest levels of sodium exposure. Results were similar for participants with or without hypertension, but the former group showed a steeper decrease in BP after sodium reduction. Intervention duration (≥12 weeks versus 4 to 11 weeks), type of study design (parallel or crossover), use of antihypertensive medication, and participants’ sex had little influence on the BP effects of sodium reduction. Additional analyses based on the BP effect of difference in sodium exposure between study arms at the end of the trial confirmed the results on the basis of achieved sodium intake. Conclusions: In this dose–response analysis of sodium reduction in clinical trials, we identified an approximately linear relationship between sodium intake and reduction in both systolic and diastolic BP across the entire range of dietary sodium exposure. Although this occurred independently of baseline BP, the effect of sodium reduction on level of BP was more pronounced in participants with a higher BP level.

scholarly journals Sodium Intake and Hypertension

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1970 ◽  
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.

scholarly journals Effects of AT1A receptor deletion on blood pressure and sodium excretion during altered dietary salt intake

2002 ◽  
Vol 283 (3) ◽  
pp. F447-F453 ◽  
Author(s):  
Amy J. Mangrum ◽  
R. Ariel Gomez ◽  
Victoria F. Norwood
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Sodium Balance ◽  
Wild Type ◽  
Compensatory Mechanisms ◽  
Wide Range ◽  
Blood Pressures ◽  
Pressure Natriuresis

The present study was performed to investigate the role of type 1A ANG II (AT1A) receptors in regulating sodium balance and blood pressure maintenance during chronic dietary sodium variations in AT1A receptor-deficient (−/−) mice. Groups of AT1A (−/−) and wild-type mice were placed on a low (LS)-, normal (NS)-, or high-salt (HS) diet for 3 wk. AT1A(−/−) mice on an LS diet had high urinary volume and low blood pressure despite increased renin and aldosterone levels. On an HS diet, (−/−) mice demonstrated significant diuresis, yet blood pressure increased to levels greater than control littermates. There was no effect of dietary sodium intake on systolic blood pressures in wild-type animals. The pressure-natriuresis relationship in AT1A (−/−) mice demonstrated a shift to the left and a decreased slope compared with wild-type littermates. These studies demonstrate that mice lacking the AT1A receptor have blood pressures sensitive to changes in dietary sodium, marked alterations of the pressure-natriuresis relationship, and compensatory mechanisms capable of maintaining normal sodium balance across a wide range of sodium intakes.

Salt and cardiovascular disease: insufficient evidence to recommend low sodium intake

2020 ◽  
Vol 41 (35) ◽  
pp. 3363-3373 ◽  
Author(s):  
Martin O’Donnell ◽  
Andrew Mente ◽  
Michael H Alderman ◽  
Adrian J B Brady ◽  
Rafael Diaz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Cardiovascular Events ◽  
Sodium Intake ◽  
Dietary Factors ◽  
Dietary Sodium ◽  
Current Evidence ◽  
Current Guideline ◽  
Current Recommendation ◽  
Low Sodium

Abstract Several blood pressure guidelines recommend low sodium intake (<2.3 g/day, 100 mmol, 5.8 g/day of salt) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence. These guidelines have been developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals, and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake and suggests that a specific low sodium intake target (e.g. <2.3 g/day) for individuals may be unfeasible, of uncertain effect on other dietary factors and of unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world’s population consume a moderate range of dietary sodium (2.3–4.6g/day; 1–2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day. While current evidence has limitations, and there are differences of opinion in interpretation of existing evidence, it is reasonable, based upon observational studies, to suggest a population-level mean target of <5 g/day in populations with mean sodium intake of >5 g/day, while awaiting the results of large randomized controlled trials of sodium reduction on incidence of cardiovascular events and mortality.

Evaluation of methods used to assess dietary intake: simulation analyses

1986 ◽  
Vol 64 (6) ◽  
pp. 772-780 ◽  
Author(s):  
George H. Beaton ◽  
Anne Chery
Keyword(s):  
Blood Pressure ◽  
Sodium Intake ◽  
Simulation Modelling ◽  
Epidemiologic Studies ◽  
Dietary Sodium ◽  
General Level ◽  
Food Frequency ◽  
Food Recalls ◽  
The Relationship ◽  
Evaluation Of Methods

The choice of dietary methodology can affect the ability to detect and describe the relationship between dietary sodium intake and blood pressure. This is illustrated in this paper through the use of simulation modelling of the effect of using different dietary methods (food recalls or records covering different numbers of days, food frequency questionnaire estimates of a single diet component) and using urinary excretion as a proxy for intake. Both epidemiologic studies and experimental interventions are simulated. Although the data base used was simulated rather than real, an attempt was made to keep it realistic in relation to what might be seen in actual populations. From these analyses it can be inferred that with appropriate choice of methodology and study design, even low order relationships between sodium intake and blood pressure should be detectable. At a more general level, it may be concluded that while there is no perfect dietary methodology, there are preferred methodologies for defined purposes.

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