About one third of the population worldwide is supposed to be salt sensitive which is a major cause for arterial hypertension later in life. For preventive actions it is thus desirable to identify salt-sensitive individuals before the appearance of clinical symptoms. Recent observations suggest that the vascular endothelium consists of two salt-sensitive barriers in series, the glycocalyx that buffers sodium and the endothelial cell membrane that contains sodium channels. Glycocalyx sodium buffer capacity and sodium channel activity are conversely related to each other. For proof of concept, a so-called salt provocation test (SPT) was developed that should unmask vascular salt sensitivity in humans at virtually any age. Nineteen healthy subjects, ranging from 25 to 63 years of age, underwent two series of 1-h blood pressure measurements after acute ingestion of a salt cocktail with or without addition of a sodium channel blocker effective in vascular endothelium. Differential analysis of the changes in diastolic blood pressure (net ∆DP) identified 12 individuals (63 %) as being salt resistant (net ∆DP = −0.05 ± 0.62 mmHg) and seven individuals (37 %) as being salt sensitive (net ∆DP = +6.98 ± 0.75 mmHg). Vascular salt sensitivity was not related to the age of the study participants. It is concluded that the SPT could be useful for identifying vascular salt sensitivity in humans already early in life.
Epithelial sodium channel (ENaC); Amiloride; Hypertension; Endothelial glycocalyx; Salt provocation test
This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging.
Endothelial glycocalyx; Endothelial surface layer; Heparan sulfate; Hyaluronic acid; Vascular disease; Optical imaging; Two-photon microscopy
Endothelial glycocalyx perturbation contributes to increased vascular permeability. In the present study we set out to evaluate whether: (1) glycocalyx is perturbed in individuals with type 2 diabetes mellitus, and (2) oral glycocalyx precursor treatment improves glycocalyx properties.
Male participants with type 2 diabetes (n = 10) and controls (n = 10) were evaluated before and after 2 months of sulodexide administration (200 mg/day). The glycocalyx dimension was estimated in two different vascular beds using sidestream dark field imaging and combined fluorescein/indocyanine green angiography for sublingual and retinal vessels, respectively. Transcapillary escape rate of albumin (TERalb) and hyaluronan catabolism were assessed as measures of vascular permeability.
Both sublingual dimensions (0.64 [0.57–0.75] μm vs 0.78 [0.71–0.85] μm, p < 0.05, medians [interquartile range]) and retinal glycocalyx dimensions (5.38 [4.88–6.59] μm vs 8.89 [4.74–11.84] μm, p < 0.05) were reduced in the type 2 diabetes group compared with the controls whereas TERalb was increased (5.6 ± 2.3% vs 3.7 ± 1.7% in the controls, p < 0.05). In line with these findings, markers of hyaluronan catabolism were increased with diabetes (hyaluronan 137 ± 29 vs 81 ± 8 ng/ml and hyaluronidase 78 ± 4 vs 67 ± 2 U/ml, both p < 0.05). Sulodexide increased both the sublingual and retinal glycocalyx dimensions in participants with diabetes (to 0.93 [0.83–0.99] μm and to 5.88 [5.33–6.26] μm, respectively, p < 0.05). In line, a trend towards TERalb normalisation (to 4.0 ± 2.3%) and decreases in plasma hyaluronidase (to 72 ± 2 U/ml, p < 0.05) were observed in the diabetes group.
Type 2 diabetes is associated with glycocalyx perturbation and increased vascular permeability, which are partially restored following sulodexide administration. Further studies are warranted to determine whether long-term treatment with sulodexide has a beneficial effect on cardiovascular risk.
www.trialregister.nl NTR780/http://isrctn.org ISRCTN82695186
An unrestricted Novartis Foundation for Cardiovascular Excellence grant (2006) to M. Nieuwdorp/E. S. G. Stroes, Dutch Heart Foundation (grant number 2005T037)
Diabetes mellitus type 2; Endothelial glycocalyx; Hyaluronan; Sulodexide; Vascular permeability
Vascular endothelium plays a key role in blood pressure regulation. Recently, it has been shown that a 5% increase of plasma sodium concentration (sodium excess) stiffens endothelial cells by about 25%, leading to cellular dysfunction. Surface measurements demonstrated that the endothelial glycocalyx (eGC), an anionic biopolymer, deteriorates when sodium is elevated. In view of these results, a two-barrier model for sodium exiting the circulation across the endothelium is suggested. The first sodium barrier is the eGC which selectively buffers sodium ions with its negatively charged prote-oglycans.The second sodium barrier is the endothelial plasma membrane which contains sodium channels. Sodium excess, in the presence of aldosterone, leads to eGC break-down and, in parallel, to an up-regulation of plasma membrane sodium channels. The following hypothesis is postulated: Sodium excess increases vascular sodium permeability. Under such con-ditions (e.g. high-sodium diet), day-by-day ingested sodium, instead of being readily buffered by the eGC and then rapidly excreted by the kidneys, is distributed in the whole body before being finally excreted. Gradually, the sodium overload damages the organism.
Aldosterone; atomic force microscopy; endothelial dysfunction; endothelial glycocalyx; epithelial sodium channel; hypertension; mechanical stiffness; salt intake; spironolactone; stiff endothelial cell syndrome
Several mechanisms have been proposed for salt-sensitive hypertension with most focusing on impaired renal sodium handling. We tested the hypothesis that abnormalities in peripheral vascular responsiveness to angiotensin-II might also exist in salt-sensitive hypertension because of the interplay of the renin-angiotensin system and dietary sodium.
Blood pressure response to angiotensin-II infusion was studied in 295 hypertensives and 165 normotensives after 7 days of high (200 mEq/day) and low (10 mEq/day) dietary sodium.
Normotensives demonstrated higher blood pressure response to angiotensin-II on high-salt than low-salt diet whereas hypertensives had similar responses on both diets, i.e., the high-salt response was not enhanced compared to low-salt. Additionally, hypertensives had a significantly greater high-salt blood pressure response to norepinephrine than to angiotensin-II. There was no correlation between the high-salt hormone levels and the difference in blood pressure response to angiotensin-II between the two diets. When stratified by blood pressure response to dietary salt restriction, individuals with salt sensitivity of blood pressure demonstrated abnormal high-salt blood pressure responsiveness to angiotensin-II. To assess if this represented increased tissue renin-angiotensin system activity in the vasculature, blood pressure responses to angiotensin were compared before and after captopril in 20 hypertensives on a high-salt diet. Subjects with the greatest blood pressure lowering effect to captopril had similar high and low-salt blood pressure responses to angiotensin-II at baseline and a significant increase in the high-salt response after captopril.
Hypertensives have an abnormal vascular response to angiotensin-II infusion on a high-salt diet. Dysregulated tissue renin-angiotensin system activity may play a role in this abnormal response. These findings raise an intriguing novel possibility for the pathophysiologic mechanism of salt-sensitive hypertension.
hypertension; salt sensitivity; salt-sensitive; sodium; angiotensin II response; tissue renin-angiotensin system
Hypertension is a leading contributor to cardiovascular mortality worldwide. Despite this, its underlying mechanism(s) and the role of excess salt in cardiorenal dysfunction are unclear. Previously, we have identified cross-talk between mineralocorticoid receptor (MR), a nuclear transcription factor regulated by the steroid aldosterone, and the small GTPase Rac1, which is implicated in proteinuric kidney disease. We here show that high-salt loading activates Rac1 in the kidneys in rodent models of salt-sensitive hypertension, leading to blood pressure elevation and renal injury via an MR-dependent pathway. We found that a high-salt diet caused renal Rac1 upregulation in salt-sensitive Dahl (Dahl-S) rats and downregulation in salt-insensitive Dahl (Dahl-R) rats. Despite a reduction of serum aldosterone levels, salt-loaded Dahl-S rats showed increased MR signaling in the kidneys, and Rac1 inhibition prevented hypertension and renal damage with MR repression. We further demonstrated in aldosterone-infused rats as well as adrenalectomized Dahl-S rats with aldosterone supplementation that salt-induced Rac1 and aldosterone acted interdependently to cause MR overactivity and hypertension. Finally, we confirmed the key role of Rac1 in modulating salt susceptibility in mice lacking Rho GDP–dissociation inhibitor α. Therefore, our data identify Rac1 as a determinant of salt sensitivity and provide insights into the mechanism of salt-induced hypertension and kidney injury.
The reflection coefficient was originally introduced by Staverman to describe the movement of nonelectrolytes through membranes. When this coefficient is extended to salts, one has a choice of defining this term for the whole salt moving as a single electrically neutral component or for the individual ions of the salt. The latter definition is meaningful only in the absence of an electric field across the permeability barrier. This condition may be achieved with the voltage clamp or short-circuit technique and is especially useful in dealing with biological systems in which one rarely has only a single salt or even equal concentrations of the major anion and cation. The relations between the transport coefficients for the salt and its individual ions are derived. The special conditions which may result in negative osmosis through a charged membrane in the presence of a salt are discussed.
The Dahl salt-sensitive rat, but not the Dahl salt-resistant rat, develops hypertension and hypovitaminosis D when fed a high salt diet. Since the salt-sensitive rat and salt-resistant rat were bred from the Sprague Dawley rat, the aim of this research was to test the hypothesis that salt-resistant and Sprague Dawley rats would be similar in their vitamin D endocrine system response to high salt intake.
Sprague Dawley, salt-sensitive, and salt-resistant rats were fed high (80 g/kg, 8%) or low (3 g/kg, 3%) salt diets for three weeks. The blood pressure of Sprague Dawley rats increased from baseline to week 3 during both high and low salt intake and the mean blood pressure at week 3 of high salt intake was higher than that at week 3 of low salt intake (P < 0.05). Mean plasma 25-hydroxyvitamin D concentrations (marker of vitamin D status) of Sprague Dawley, salt-sensitive, and salt-resistant rats were similar at week 3 of low salt intake. Mean plasma 25-hydroxyvitamin D concentrations of Sprague Dawley and salt-resistant rats were unaffected by high salt intake, whereas the mean plasma 25-hydroxyvitamin D concentration of salt-sensitive rats at week 3 of high salt intake was only 20% of that at week 3 of low salt intake.
These data indicate that the effect of high salt intake on the vitamin D endocrine system of Sprague Dawley rats at week 3 was similar to that of salt-resistant rats. The salt-sensitive rat, thus, appears to be a more appropriate model than the Sprague Dawley rat for assessing possible effects of salt-sensitivity on vitamin D status of humans.
Reducing salt intake is known to be an important factor for lowering blood pressure and preventing cardiovascular disease. Estimating amount of salt intake is a necessary step towards salt intake reduction. Self-reported saltiness of diet is a method most easily used to measure a patient's salt intake. The purpose of this study was to examine the value of self-reported saltiness of diet in measuring salt intake.
We used data from 681 participants who visited a health center at a university hospital between August 2003 and November 2005. A self-administered questionnaire was used to collect information on self-reported saltiness of diet, other dietary habits and lifestyle factors. Salt intake was estimated on the basis of 24-hour dietary recall with a computer-aided nutritional analysis program (CAN-Pro 2.0, Korean Nutrition Society).
There was no statistically significant difference between the mean salt intake of the self-reported salty diet group (13.7 ± 4.8 g/d) and the self-reported unsalty diet group (13.3 ± 4.4 g/d). If we assume calculated salt intake as the gold standard, the sensitivity and specificity of self-reported saltiness were 39.5% and 63.6%, respectively. Salt intake was increased with higher calorie intake, frequency of eating breakfast (≥5 times/wk) and being satiated with usual diet in men, but it was increased only with higher calorie intake in women. Regardless of actual salt intake, the group satiated with a usual diet tended to be in the group of self-reported salty diet.
Self-reported saltiness of diet was not associated with actual salt intake. Further studies will be needed on the simpler and more objective tools to estimate salt intake.
Saltiness; Salt Intake; Self Report; Diet Records
This brief review deals with some novel developments regarding the possible role of salt in the pathogenesis of cardiovascular and renal disorders. Studies in both humans and experimental animals are discussed. Increased salt intake is usually associated with an increase in arterial pressure although some controversies still exist. Salt sensitivity of arterial pressure (defined as an increase in arterial pressure on dietary salt overload) was demonstrated in many animal species as well as in humans. However, findings in rats, the most often used animal model, also demonstrated that this salt sensitivity was not uniform; some strains are salt sensitive, while other strains are salt resistant. Salt sensitivity of arterial pressure in humans is also not uniform; less than one-third of normotensive individuals and less than one-half of hypertensive individuals are salt sensitive. Of great importance are findings that excessive salt intake may damage target organs (cardiovascular system and kidneys) irrespective of arterial pressure. Together with an ever-growing consensus that sodium intake in acculturated societies is high, these findings also emphasize the need for reduction in salt intake. Therefore, the adverse cardiovascular and renal effects of salt continue to be a subject of intense study. Current data indicate that a reduction in salt intake should ameliorate, if not prevent, cardiovascular and renal morbidity and mortality, particularly among individuals with hypertension.
Cardiovascular injury; heart; hypertension; kidney; salt
Chronically elevated plasma angiotensin II (AngII) causes a salt-sensitive form of hypertension that is associated with a differential pattern of peripheral sympathetic outflow. This “AngII-salt sympathetic signature” is characterized by a transient reduction in sympathetic nervous system activity (SNA) to the kidneys, no change in SNA to skeletal muscle, and a delayed activation of SNA to the splanchnic circulation. Studies suggest that the augmented sympathetic influence on the splanchnic vascular bed increases vascular resistance and decreases vascular capacitance, leading to hypertension via translocation of blood volume from the venous to the arterial circulation. This unique sympathetic signature is hypothesized to be generated by a balance of central excitatory inputs and differential baroreceptor inhibitory inputs to sympathetic premotor neurons in the rostral ventrolateral medulla. The relevance of these findings to human hypertension and the future development of targeted sympatholytic therapies are discussed.
Neurogenic hypertension; Sympathetic nerve activity; Salt; Angiotensin II; Splanchnic nerve activity
Angiotensin II (AngII) – induced hypertension in experimental animals has been proposed to be due in part to activation of the sympathetic nervous system. This sympathetic activation appears to be accentuated in animals consuming a high salt diet (AngII-salt hypertension). However, accurate quantification of sympathetic activity is difficult and controversy remains. A particularly important question is: What are the critical vascular beds targeted by increased sympathetic nerve activity (SNA) in AngII-salt hypertension? To address this issue, mean arterial pressure (MAP) and renal (RSNA) or lumbar SNA (LSNA) were continuously recorded during a 5 day control period, 11 days of AngII (150 ng/kg/min, sc) and a 5 day recovery period in conscious rats on a high salt (2% NaCl) diet. Whereas MAP reached a new steady-state level of 30-35 mmHg above control levels by the end of the AngII period, RSNA decreased by 40% during the first 7 days of AngII and then returned towards control levels by day 10 of AngII. In contrast, LSNA remained at control levels throughout the AngII period. In another experiment we measured hindlimb norepinephrine (NE) spillover in conscious rats on normal (0.4%) or high (2.0%) salt diets before and during 14 days of AngII administration. AngII had no significant affect on hindlimb NE spillover in either group. We conclude that chronic AngII modulates renal and lumbar SNA differentially in rats consuming a high salt diet and that AngII-salt hypertension in the rat is not caused by increased SNA to the renal or hindlimb vascular beds.
hypertension; renal nerve activity; lumbar nerve activity; norepinephrine spillover; sympathetic
Enterotoxin preparations derived from Escherichia coli strain H-10407 were shown to contain vascular permeability factor (PF) activity as well as diarrheagenic activity. Intradermal injection of E. coli enterotoxin (ECT) caused localized induration and permeability of small blood vessels of the skin to intravenously administered Evans blue dye. The PF assay described here demonstrated a linear dose response and was at least as sensitive as the adult rabbit ileal loop assay for detecting ECT. E. coli PF activity was heat labile and was neutralized by homologous antiserum. PF production was enhanced by the addition of yeast extract (up to 0.6%) to a Casamino Acids-salts medium. PF activity was detectable as early as 6 h in aerated (shake) cultures in the Casamino Acids-yeast extract-salts medium, pH 8.5, maximal at 18 h and essentially unchanged at 48 h. The skin test (PF) assay for ECT has numerous advantages over current assay methods which involve gastrointestinal challenge of experimental animals.
Aldosterone, one of the major culprits associated with the renin-angiotensin-aldosterone system (RAAS), is significantly elevated following high salt administration in Dahl rats. Since we have previously demonstrated that aldosterone (ALDO) upregulates cyclooxygenase (COX) expression in the kidney, the present study was design to assess whether prostaglandin release is involved in the effects of chronic aldosterone treatment on vascular function of the aorta from nonhypertensive Dahl salt-sensitive rats.
The effects of aldosterone on arachidonic acid metabolism and on the expression of cyclooxygenase (COX)-2 were evaluated in the Dahl salt sensitive (DS) rat aorta, renal, femoral and carotid arteries. DS rats on a low salt (0.3% NaCl) diet were treated with or without ALDO for four weeks. Indirect blood pressure (BP), the release of prostacyclin (PGI2) and prostaglandin E2, and the expression of COX-2 were measured to assess the vascular remodelling by aldosterone. Vascular function was also assessed by contractile responsiveness in the aorta to phenylephrine. ALDO increased BP (17 ± 1%) and inhibited the basal release of PGE2. ALDO enhanced vascular reactivity to phenylephrine and up regulated the expression of COX-2 in both aorta and renal vessels but reduced COX-2 expression in the femoral artery.
These data reveal that the effect of ALDO in the vasculature is tissue specific and may involve the inhibition of PGE2 release. Thus, suggesting a role for prostaglandins in the vasculopathic aspects of aldosterone.
Sodium overload stiffens vascular endothelial cells in vitro and promotes arterial hypertension in vivo. The hypothesis was tested that the endothelial glycocalyx (eGC), a mesh of anionic biopolymers covering the surface of the endothelium, participates in the stiffening process. By using a mechanical nanosensor, mounted on an atomic force microscope, height (∼400 nm) and stiffness (∼0.25 pN/nm) of the eGC on the luminal endothelial surface of split-open human umbilical arteries were quantified. In presence of aldosterone, the increase of extracellular sodium concentration from 135 to 150 mM over 5 days (sodium overload) led the eGC shrink by ∼50% and stiffening by ∼130%. Quantitative eGC analyses reveal that sodium overload caused a reduction of heparan sulphate residues by 68% which lead to destabilization and collapse of the eGC. Sodium overload transformed the endothelial cells from a sodium release into a sodium-absorbing state. Spironolactone, a specific aldosterone antagonist, prevented these changes. We conclude that the endothelial glycocalyx serves as an effective buffer barrier for sodium. Damaged eGC facilitates sodium entry into the endothelial cells. This could explain endothelial dysfunction and arterial hypertension observed in sodium abuse.
Endothelium; Aldosterone; Vascular dysfunction; Sodium channel; Sodium
The endocytosis of horseradish peroxidase (HRP) by the vascular cells of retinal and choroidal blood vessels was compared in immersion and perfusion fixed eyes from individual rats. The mechanisms of endocytosis of HRP appeared identical in both retinal and choroidal vessels. The bulk of internalised tracer occurred in macropinosomes 300-400 nm in diameter. Tracer was localised to a 20-30 nm layer on the internal aspect of the limiting membrane. This layer was coincident with the glycocalyx of the luminal plasma membrane as revealed by ruthenium redosmium tetroxide staining. Horseradish peroxidase was also internalised by a small scattered population of vesicles (100-130 nm in diameter). The size of these vesicles suggested that they may have arisen from clathrin coated regions of the plasma membrane. It is suggested that the endocytosis of HRP in retinal and choroidal vascular endothelium occurs as a function of plasma membrane recycling. Horseradish peroxidase may also be internalised as a 'contaminant' of the glycocalyx in coated pits involved in receptor mediated endocytosis. The smooth 80 nm plasmalemmal caveolae of the retinal and choroidal vascular endothelial cells did not appear to participate either in absorptive endocytosis or vesicular transport.
Salt-sensitive hypertension is common in the aged population. Increased fruit and vegetable intake reduces hypertension, but its effect on eventual diastolic dysfunction is unknown. This relationship is tested in the Dahl Salt-Sensitive (Dahl-SS) rat model of salt-sensitive hypertension and diastolic dysfunction. Table grape powder contains phytochemicals that are relevant to human diets. For 18 weeks, male Dahl-SS rats were fed one of five diets: low salt (LS), a low salt + grape powder (LSG), high salt (HS), a high salt grape powder (HSG), or high salt vasodilator hydralazine (HSH). Compared to the HS diet,the HSG diet lowered blood pressure and improved cardiac function; reduced systemic inflammation; reduced cardiac hypertrophy, fibrosis, and oxidative damage; and increased cardiac glutathione. The HSH diet similarly reduced blood pressure but did not reduce cardiac pathogenesis. The LSG diet reduced cardiac oxidative damage and increased cardiac glutathione. In conclusion, physiologically relevant phytochemical intake reduced salt-sensitive hypertension and diastolic dysfunction.
Heart failure; Diet; Fruits; Vegetables
The ingestion of excess dietary salt (defined as NaCl) is strongly correlated with cardiovascular disease, morbidity, mortality, and is regarded as a major contributing factor to the pathogenesis of hypertension. Although several mechanisms contribute to the adverse consequences of dietary salt intake, accumulating evidence suggest that dietary salt loading produces neurogenically-mediated increases in total peripheral resistance to raise arterial blood pressure (ABP). Evidence from clinical studies and experimental models clearly establish a hypertensive effect of dietary salt loading in a subset of individuals who are deemed “salt-sensitive”. However, we will discuss and present evidence to develop a novel hypothesis to suggest that while chronic increases in dietary salt intake do not elevate mean ABP in “non-salt-sensitive” animals, dietary salt intake does enhance several sympathetic reflexes thereby predisposing these animals and/or individuals to the development of salt-sensitive hypertension. Additional evidence raises an intriguing hypothesis that these enhanced sympathetic reflexes are largely attributed to the ability of excess dietary salt intake to selectively enhance the excitability of sympathetic-regulatory neurons in the rostral ventrolateral medulla. Insight into the cellular mechanisms by which dietary salt intake alters the responsiveness of RVLM circuits will likely provide a foundation for developing new therapeutic approaches to treat salt-sensitive hypertension.
dietary salt; blood pressure; sympathetic; rostral ventrolateral medulla; salt-sensitivity; hypertension
Marine pseudomonads, such as Pseudomonas atlantica, are readily isolated from sediments. These organisms form extracellular polysaccharide polymers (glycocalyx). The factors affecting the composition and amount of glycocalyx in batch culture of these organisms were examined. The formation of glycocalyx was stimulated by the inclusion of galactose as the carbon source and by increased surface area resulting from addition of sand to the medium. The composition of the glycocalyx changed during the growth cycle, with a marked increase in the proportions and absolute amounts of uronic acids as the rate of synthesis increased. In estuarine sediments, the glycocalyx contained a carbon content at least as great as in the microbes themselves. The greatest accumulation of these polymers occurred late in the stationary phase when the physiological status of the cells, as measured by the adenylate energy charge, showed maximal stress. Maximal formation of glycocalyx possibly could be used as an estimate of the nutritional status of these microbes.
Excessive sodium intake leading to hypertension, stroke, and stomach cancer is mainly caused by excess use of salt in cooking. This study was performed to estimate the salt content in school meals and to compare differences in perceptions related to sodium intake between students and staffs working for school meal service. We collected 382 dishes for food from 24 schools (9 elementary, 7 middle, 8 high schools) in Gyeonggi-do and salt content was calculated from salinity and weight of individual food. The average salt content from elementary, middle, and high school meals were 2.44 g, 3.96 g, and 5.87 g, respectively. The amount of salt provided from the school lunch alone was over 80% of the recommended daily salt intake by WHO. Noodles, stews, sauces, and soups were major sources of salt intake at dish group level, while the most salty dishes were sauces, kimchies, and stir-fried foods. Dietary knowledge and attitude related to sodium intake and consumption frequency of the salty dishes were surveyed with questionnaire in 798 students and 256 staffs working for school meal service. Compared with the staffs, the students perceived school meals salty and the proportions of students who thought school meals were salty increased with going up from elementary to high schools (P < 0.001). Among the students, middle and high school students showed significant propensity for the preference to one-dish meal, processed foods, eating much broth and dipping sauce or seasoning compared with the elementary students, although they had higher nutrition knowledge scores. These results proposed that monitoring salt content of school meals and consideration on the contents and education methods in school are needed to lower sodium intake.
School meal; salt content; sodium intake; saltiness perception
Purpose of review
Investigation into the underlying mechanisms of salt sensitivity has made important advances in recent years. This review examines in particular the effects of sodium and potassium on vascular function.
Sodium chloride (salt) intake promotes cutaneous lymphangiogenesis mediated through tissue macrophages and directly alters endothelial cell function, promoting increased production of transforming growth factor-β (TGF-β) and nitric oxide (NO). In the setting of endothelial dysfunction, such as occurs with aging, diminished NO production exacerbates the vascular effects of TGF-β, promoting decreased arterial compliance and hypertension. Dietary potassium intake may serve as an important countervailing influence on the effects of salt in the vasculature.
There is growing appreciation that, independently of alterations in blood pressure, dietary intake of sodium and potassium promote functional changes in the vasculature and lymphatic system. These changes may serve as compensatory changes that protect against development of salt-sensitive hypertension. While salt sensitivity cannot be ascribed exclusively to these factors, perturbation of these processes promote hypertension during high-salt intake. These studies add to the list of genetic and environmental factors that are associated with salt sensitivity, but in particular provide insight into adaptive mechanisms during high salt intake.
dietary sodium; dietary potassium; nitric oxide; TGF-β; arterial compliance
The importance of excess salt intake in the pathogenesis of hypertension is widely recognized. Blood pressure is controlled primarily by salt and water balance because of the infinite gain property of the kidney to rapidly eliminate excess fluid and salt. Up to fifty percent of patients with essential hypertension are salt-sensitive, as manifested by a rise in blood pressure with salt loading. We conducted a two-stage genetic analysis in hypertensive patients very accurately phenotyped for their salt-sensitivity. All newly discovered never treated before, essential hypertensives underwent an acute salt load to monitor the simultaneous changes in blood pressure and renal sodium excretion. The first stage consisted in an association analysis of genotyping data derived from genome-wide array on 329 subjects. Principal Component Analysis demonstrated that this population was homogenous. Among the strongest results, we detected a cluster of SNPs located in the first introns of PRKG1 gene (rs7897633, p = 2.34E-05) associated with variation in diastolic blood pressure after acute salt load. We further focused on two genetic loci, SLC24A3 and SLC8A1 (plasma membrane sodium/calcium exchange proteins, NCKX3 and NCX1, respectively) with a functional relationship with the previous gene and associated to variations in systolic blood pressure (the imputed rs3790261, p = 4.55E-06; and rs434082, p = 4.7E-03). In stage 2, we characterized 159 more patients for the SNPs in PRKG1, SLC24A3 and SLC8A1. Combined analysis showed an epistatic interaction of SNPs in SLC24A3 and SLC8A1 on the pressure-natriuresis (p interaction = 1.55E-04, p model = 3.35E-05), supporting their pathophysiological link in cellular calcium homeostasis. In conclusions, these findings point to a clear association between body sodium-blood pressure relations and molecules modulating the contractile state of vascular cells through an increase in cytoplasmic calcium concentration.
The root system is particularly affected by unfavorable conditions because it is in direct contact with the soil environment. Casparian strips, a specialized structure deposited in anticlinal walls, are characterized by the impregnation of the primary wall pores with lignin and suberin. The Casparian strips in the endo- and exodermis of vascular plant roots appear to play an important role in preventing the non-selective apoplastic bypass of salts into the stele along the apoplast under salt stress. However, only a few investigations have examined the deposition and function of these apoplastic barriers in response to salt stress in higher plants.
Casparian strip; chemical components; development; root
Salt retention as a result of chronic, excessive dietary salt intake, is widely accepted as one of the most common causes of hypertension. In a small minority of cases, enhanced Na+ reabsorption by the kidney can be traced to specific genetic defects of salt transport, or pathological conditions of the kidney, adrenal cortex, or pituitary. Far more frequently, however, the salt retention may be the result of minor renal injury or small genetic variation in renal salt transport mechanisms. How the salt retention actually leads to the increase in peripheral vascular resistance (the hallmark of hypertension) and the elevation of blood pressure remain an enigma. Here we review the evidence that endogenous ouabain (an adrenocortical hormone), arterial smooth muscle α2 Na+ pumps, type-1 Na/Ca exchangers, and receptor- and store-operated Ca2+ channels play key roles in the pathway that links salt to hypertension. We discuss cardenolide structure-function relationships in an effort to understand why prolonged administration of ouabain, but not digoxin, induces hypertension, and why digoxin is actually anti-hypertensive. Finally, we summarize recent observations which indicate that ouabain upregulates arterial myocyte Ca2+ signaling mechanisms that promote vasoconstriction, while simultaneously downregulating endothelial vasodilator mechanisms. In sum, the reports reviewed here provide novel insight into the molecular mechanisms by which salt retention leads to hypertension.
Salt-dependent hypertension; Calcium; Sodium Pump; Sodium/Calcium Exchanger; Receptor-operated Channel
The blood-brain barrier (BBB) impedes the influx of intravascular compounds from the blood to the brain. Few blood-borne macromolecules are transferred into the brain because vesicular transcytosis in the endothelial cells is considerably limited and the tight junction is located between the endothelial cells. At the first line of the BBB, the endothelial glycocalyx which is a negatively charged, surface coat of proteoglycans, and adsorbed plasma proteins, contributes to the vasculoprotective effects of the vessels wall and are involved in maintaining vascular permeability. In the endothelial cytoplasm of cerebral capillaries, there is an asymmetrical array of metabolic enzymes such as alkaline phosphatase, acid phosphatase, 5’-nucleotidase, adenosine triphosphatase, and nucleoside diphosphatase and these enzymes contribute to inactivation of substrates. In addition, there are several types of influx or efflux transporters at the BBB, such as P-glycoprotein (P-gp), multidrug resistance associated protein, breast cancer resistance protein, organic anion transporters, organic cation transporters, organic cation transporter novel type transporters, and monocarboxylic acid transporters. P-gp, energy-dependent efflux transporter protein, is instrumental to the barrier function. Several findings recently reported indicate that endothelial P-gp contributes to efflux of undesirable substances such as β-amyloid protein from the brain or periarterial interstitial fluid, while P-gp likely plays a crucial role in the genesis of multiple vascular abnormalities that accompany hypertension. In this review, influx and efflux mechanisms of drugs at the BBB are also reviewed and how medicines pass the BBB to reach the brain parenchyma is discussed.
Blood-brain barrier; P-glycoprotein; tight junction.