Changes In Salt Intake Research Articles

Altered dietary salt intake for people with chronic kidney disease.

Salt intake shows great promise as a modifiable risk factor for reducing heart disease incidence and delaying kidney function decline in people with chronic kidney disease (CKD). However, a clear consensus of the benefits of reducing salt in people with CKD is lacking. This review evaluated the benefits and harms of altering dietary salt intake in people with CKD. We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We included randomised controlled trials (RCTs) that compared two or more levels of salt intake in people with any stage of CKD. Two authors independently assessed studies for eligibility and conducted risk of bias evaluation. Results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Mean effect sizes were calculated using the random-effects models. We included eight studies (24 reports, 258 participants). Because duration of the included studies was too short (1 to 26 weeks) to test the effect of salt restriction on endpoints such as mortality, cardiovascular events or CKD progression, changes in salt intake on blood pressure and other secondary risk factors were applied. Three studies were parallel RCTs and five were cross-over studies. Selection bias was low in five studies and unclear in three. Performance and detection biases were low in two studies and unclear in six. Attrition and reporting biases were low in four studies and unclear in four. One study had the potential for high carryover effect; three had high risk of bias from baseline characteristics (change of medication or diet) and two studies were industry funded.There was a significant reduction in 24 hour sodium excretion associated with low salt interventions (range 52 to 141 mmol) (8 studies, 258 participants: MD -105.86 mmol/d, 95% CI -119.20 to -92.51; I(2) = 51%). Reducing salt intake significantly reduced systolic blood pressure (8 studies, 258 participants: MD -8.75 mm Hg, 95% CI -11.33 to -6.16; I(2) = 0%) and diastolic blood pressure (8 studies, 258 participants: MD -3.70 mm Hg, 95% CI -5.09 to -2.30; I(2) = 0%). One study reported restricting salt intake reduced the risk of oedema by 56%. Salt restriction significantly increased plasma renin activity (2 studies, 71 participants: MD 1.08 ng/mL/h, 95% CI 0.51 to 1.65; I(2) = 0%) and serum aldosterone (2 studies, 71 participants: 6.20 ng/dL (95% CI 3.82 to 8.58; I(2) = 0%). Antihypertensive medication dosage was significantly reduced with a low salt diet (2 studies, 52 participants): RR 5.48, 95% CI 1.27 to 23.66; I(2) = 0%). There was no significant difference in eGFR (2 studies, 68 participants: MD -1.14 mL/min/1.73 m(2), 95% CI -4.38 to 2.11; I(2) = 0%), creatinine clearance (3 studies, 85 participants): MD -4.60 mL/min, 95% CI -11.78 to 2.57; I(2) = 0%), serum creatinine (5 studies, 151 participants: MD 5.14 µmol/L, 95% CI -8.98 to 19.26; I(2) = 59%) or body weight (5 studies, 139 participants: MD -1.46 kg; 95% CI -4.55 to 1.64; I(2) = 0%). There was no significant change in total cholesterol in relation to salt restriction (3 studies, 105 participants: MD -0.23 mmol/L, 95% CI -0.57 to 0.10; I(2) = 0%) or symptomatic hypotension (2 studies, 72 participants: RR 6.60, 95% CI 0.77 to 56.55; I(2) = 0%). Salt restriction significantly reduced urinary protein excretion in all studies that reported proteinuria as an outcome, however data could not be meta-analysed. We found a critical evidence gap in long-term effects of salt restriction in people with CKD that meant we were unable to determine the direct effects of sodium restriction on primary endpoints such as mortality and progression to end-stage kidney disease (ESKD). We found that salt reduction in people with CKD reduced blood pressure considerably and consistently reduced proteinuria. If such reductions could be maintained long-term, this effect may translate to clinically significant reductions in ESKD incidence and cardiovascular events. Research into the long-term effects of sodium-restricted diet for people with CKD is warranted, as is investigation into adherence to a low salt diet.

Living in Environments with Contrasting Salinities: A Review of Physiological and Behavioural Responses in Waterbirds

During the course of their lives many vertebrates live and forage in environments characterized by different salinities and must therefore respond to changes in salt intake. This is particularly true for numerous species of migratory waterbirds, especially those that routinely commute between saltwater and freshwater wetlands throughout their annual cycle and/or within a season. These birds have evolved a suite of morphological, physiological and behavioural mechanisms to successfully maintain osmoregulatory balance. However, relatively little is known about the impacts of salinity on the distribution, physiological performance and reproductive success of waterbirds. Here I review the current knowledge of the physiological and behavioural mechanisms through which waterbirds cope with contrasting salinities and how some of the adjustments undertaken might interfere with relevant aspects of their performance. I argue that, because of their strong reliance on wetland ecosystems for foraging and breeding, waterbirds may be particularly vulnerable to climate-induced changes in salinity, especially in arid or semiarid tropical areas where increases in both temperature and salinity may affect their body condition and, ultimately, survival prospects. I conclude by offering some suggestions for future research that could take us beyond our current level of understanding of avian osmoregulation.

Estimated urinary salt excretion by a self-monitoring device is applicable to education of salt restriction.

The objective was to investigate the validity of a self-monitoring device that estimates 24-h urinary salt excretion from overnight urine samples as a tool for education regarding salt restriction. Twenty healthy volunteers consumed test meals for 14 days, with salt content as follows: 10 g (days 1-5); 5 g (days 6-8, 12 and 14); and 13 g (days 9-11 and 13). On days 2-15, urinary salt excretion was estimated from overnight urine samples by a self-monitoring device. Twenty-four-hour urine samples were collected on days 5 and 8 to measure salt excretion directly. Blood pressure was measured in the morning and during sleep on days 1-15. Estimated urinary salt excretion measured by the device showed a correlation with salt intake, and the ratio of estimated urinary salt excretion to salt intake was 0.84±0.10 (days 2-6), 1.27±0.28 (days 7-9), 0.70±0.11 (days 10-12), 1.37±0.22 (day 13), 0.68±0.13 (day 14) and 1.33±0.19 (day 15). The correlation between estimated urinary salt excretion measured by a device and directly measured 24-h urinary salt excretion was significant (r=0.65, P<0.05) during the period of 10 g salt intake, but not during 5 g salt intake. Blood pressure in the morning was not influenced by the change in salt intake, but systolic pressure during sleep showed a significant increase or decrease according to the levels of salt intake. In conclusion, a self-monitoring device, which can estimate 24-h urinary salt excretion from overnight urine samples, is considered to be a practical tool for education regarding salt restriction, although a similar future investigation is needed in older and/or hypertensive subjects.

Sodium balance is not just a renal affair.

The equilibration theory of extracellular body fluids is tightly linked to sodium (Na) metabolism. It is accepted that with changes in salt intake, renal sodium elimination will prevent any change in interstitial Na content and concentration. This review summarizes recent anomalous findings regarding salt and water homeostasis that are inconsistent with current assumptions. Recent findings from chemical analysis studies of laboratory animals, as well as noninvasive quantitative Na MRI (Na-MRI) studies in patients, have shown that remarkable amounts of Na are stored in muscle and in skin without commensurate water retention. Furthermore, an ultra-long Na balance study in humans suggests the presence of endogenous clocks that generate weekly and monthly infradian rhythmicity of Na storage independent of salt intake. Animal experiments suggest that fluids in the skin interstitium are hypertonic compared with plasma, and that interstitial osmotic stress induces local extrarenal immune cell and lymph-capillary driven mechanisms for electrolyte clearance and maintenance of the internal environment. Recent quantitative evidence challenges current ideas on salt and water homeostasis, and suggests that Na homeostasis cannot be maintained without additional previously unappreciated extrarenal regulatory mechanisms.

Salt reduction as a population-based intervention for the prevention of coronary heart diseases: an economic assessment

<h3>Background</h3> The incidence of coronary heart diseases is increasing in the occupied Palestinian territory (oPt) and hence poses a growing challenge for treatment. Reduction in the intake of dietary salt is a potentially cost-effective approach to reduce the burden of coronary heart diseases. Here, we report the results of an economic assessment of three interventions of salt reduction in the oPt. <h3>Methods</h3> We did the analysis from a societal perspective of three salt-reduction interventions—population-wide health promotion campaigns, mandatory labelling of food packaging, and mandatory reduction of salt content of processed food. These interventions were assessed individually, and in combinations of two and all three together. We estimated the costs of policies using past experiences, expert opinion, and hospital records, and costs of health care with a standardised unit cost for treatments. We considered the financial implications for the food industry and public sectors. The total cost of implementation of each policy was compared with the do-nothing scenario. We used data reported in reviews of epidemiological studies as estimates of the expected reduction of the current sodium salt consumption attributable to each policy. The expected change in salt intake was then converted into a change in mean population blood pressure based on estimates reported in a meta-analysis. The change in blood pressure was used to estimate the number of deaths prevented or postponed in 10 years, using the Palestinian IMPACT policy model for coronary heart disease. The estimates were compared with the number of deaths from coronary heart disease that would have been expected in relation to the number in the baseline year. This policy model is an epidemiological model that was used to analyse mortality associated with coronary heart disease and risk factor trends in the West Bank, oPt, between 1998 and 2009, and project mortality trends for the future. We used Microsoft Excel 2010 for our analyses. <h3>Findings</h3> All policies resulted in a reduction in salt intake of 5–30%, leading to changes of 1–20 mm Hg in systolic blood pressure. All scenarios were cost effective compared with the do-nothing scenario. The cost-effectiveness of the scenarios for per life-year gained was $134·57–1430·62 (purchasing power parity at 2010 exchange rates). Policies for the labelling of food and use of the three interventions together were the most cost effective. These two scenarios were estimated to save costs ($9 million and $6 million) and resulted in 945 life-years gained and 2682 life-years gained, respectively. <h3>Interpretation</h3> Reduction of salt intake reduces the long-term burden of coronary heart diseases. In the oPt, population-based interventions to reduce salt intake are not only cost effective but also cost saving. We recommend a population-wide health promotion campaign, mandatory labelling of food packaging, and mandatory reduction of salt content of processed food. <h3>Funding</h3> European Community's Seventh Framework Programme.

Salt, fruit and vegetable consumption and blood pressure development: a longitudinal investigation in healthy children

Low salt intake and high fruit and vegetable intake (FVI) have been shown to reduce blood pressure (BP) in adults. Longitudinal data on the independent effect of both FVI and salt intake on BP in healthy normotensive children are not available yet. In the present study, we aimed to characterise the concomitant influence of salt intake and FVI on BP development throughout childhood and adolescence. We examined 435 healthy subjects, for whom at least three repeated measurements of BP had been taken and who had provided 24 h urine samples and 3 d weighed dietary records between 4 and 18 years of age. BP was measured using a mercury sphygmomanometer (Mercuro 300, WelchAllyn) and salt intake was determined based on 24 h Na excretion. The intra-individual change in salt intake was almost significantly associated with the change in systolic BP (SBP, P= 0·06) and marginally (P= 0·09) with that in diastolic BP (DBP) in puberty, but not in pre-puberty. A 1 g/d increase in salt intake was associated with a 0·2 mmHg increase in SBP. In pre-puberty, but not in puberty, differences in FVI between children predicted between-person variations in SBP and DBP (P= 0·03). Corresponding findings were obtained for 24 h K excretion (a urinary indicator for FVI). A 100 g/d lower FVI was related to a 0·4 mmHg higher BP value. In conclusion, in healthy children and adolescents with BP in the low-normal range, both salt intake and FVI may already start to influence BP, although at a small magnitude. The potential importance of establishing healthy eating habits in childhood for later BP development emphasises the role of higher FVI and lower salt intake in the prevention of hypertension in the long run.

Blood pressure in Afghan male immigrants to Denmark

Immigration from a Third-World society to a Western society can be associated with higher blood pressure and salt sensitivity. We therefore tested whether immigrants from Afghanistan to Denmark compared with non-immigrant Danes exhibit a (i) higher 24-h ambulatory blood pressure (24-h ABP) and (ii) blunted renin response to a change in salt intake. Twenty-four-hour ABP was measured in 40 men of Afghan (Afghans) and 40 men of Danish (Danes) origin. Each group was divided into young (20-30years, n=20) and middle aged (40-60years, n=20). A 3-day low (70mmol per 24-h) and a 3-day high (250mmol per 24-h) salt intake were in addition instituted in subgroups of the young groups (n=18). Young and middle-aged Afghans exhibited a lower 24-h mean arterial pressure (24-h MAP) than the same respective age groups of Danes (83±1 versus 90±1mm Hg, P<0·05, and 89±2 versus 100±1mm Hg, P<0·05). 24-h ABP did not change in any of the young groups during increased salt intake, whereas the Danes exhibited a greater decrease in plasma renin activity (PRA) (P<0·05). Plasma noradrenaline (PNA ) was significantly higher among the young Afghans. Afghan immigrants to Denmark exhibit a lower 24-h ABP than Danes. In young Afghans, PRA is less sensitive to changes in salt intake, while PNA is higher and may reflect their lower systolic blood pressure and/or arterial pulse pressure. Whether these hormonal differences can explain the lower 24-h ABP in Afghans should be further explored.

Validation of a self-monitoring device for estimating 24-hour urinary salt excretion.

The purpose of this study was to investigate the relationship between salt intake and urinary salt excretion and to examine the validity of a self-monitoring device for estimating 24-h urinary salt excretion from overnight urine samples. Twelve young, healthy female volunteers consumed test meals from days 1 to 14 and estimated urinary salt excretion on days 2-15 by using a self-monitoring device. The salt content of the test meals was as follows: 10 g (days 1-5), 6 g (days 6-8), 13 g (days 9-11), 6 g (day 12), 13 g (day 13), and 6 g (day 14). The average 24-h urinary salt excretion (the ratio of urinary salt excretion to salt intake of the previous day) estimated from the overnight urine samples was as follows: 8.01±1.15 g (0.73±0.11) on days 2-6, 5.86±0.85 g (1.01±0.15) on days 7-9, 9.69±1.64 g (0.74±0.13) on days 10-12, 6.51±1.56 g (1.03±0.25) on day 13, 8.60±3.25 g (0.71±0.14) on day 14, and 6.28±1.31 (1.05±0.22) on day 15. Thus, the salt excretion/salt intake ratio was approximately 0.8 during the high-salt phase and 1.0 during the low-salt phase. The estimation of 24-h urinary salt excretion from overnight urine samples by using a self-monitoring device is a reasonably valid method in this young and healthy female population for detecting daily changes in salt intake.

Salt sensitivity of blood pressure: developmental and sex-related effects

Epidemiologic studies have shown convincingly that drastically reducing salt intake in the community is accompanied by blood pressure reductions that are comparable to those achieved by antihypertensive medication. Moreover, many subjects with hypertension are salt sensitive. This implies that, in these subjects, blood pressure is more responsive to changes in salt intake than in subjects with normal blood pressure. The presence of conventional risk factors associated with the metabolic syndrome correlates with salt sensitivity. However, women appear to be more salt sensitive than men. Sparse data indicate that the salt sensitivity of blood pressure is greater in subjects with low birth weight. Experimental studies in rats have also shown that hypertensive offspring of dams maintained on low-protein diets throughout or in late pregnancy are more salt sensitive. This is accompanied by increased expression of the thick ascending limb Na-K-2Cl symporter (NKCC2). Perinatal interventions aimed at persistently lowering blood pressure in genetically hypertensive rats have consistently proven to be very effective and are often accompanied by a wave of natriuresis exclusively at 4 wk of age. In sum, in addition to conventional metabolic risk factors for cardiovascular disease, low birth weight and possibly its sequels such as catch-up growth should be viewed as modifiable risk factors for salt sensitivity of blood pressure. Female sex may also be a nonmodifiable risk factor for salt sensitivity. Experimental data indicate that NKCC2 may well be an important determinant of salt sensitivity in acquired (developmental) hypertension.

Salt and Cardio-Renal Connection

In all animal models examined whose blood pressure (BP) is sensitive to changes in salt intake, glomerular BP indeed proved elevated. In fact, we quantitatively estimated glomerular BP elevated in this type of hypertension. We also showed that BP failed to fall during night in patients with salt sensitive type of hypertension, and they manifested as non-dippers. In addition, high cardiovascular event rates were recognized in salt sensitive patients than in non-salt sensitive patients.

Decreased Salt Intake in Japanese Men Aged 40 to 70 Years and Women Aged 70 to 79 Years: An 8-Year Longitudinal Study

Background It is not known whether salt intake decreases over time in the same population. This study attempts to describe salt intake for 8 years according to age groups, and examines whether salt intake changes over time in community-dwelling middle-aged and elderly Japanese subjects. Methods Data were collected as part of the National Institute for Longevity Sciences Longitudinal Study of Aging. Participants included 544 men and 512 women who participated in and completed all nutrition surveys from the first (1997-2000) to fifth (2006-2008) study waves. Each study wave was conducted for 2 years; in individuals, the entire follow-up period was 8 years. Salt and energy intake were calculated from 3-day diet records with photographs. The mixed-effects regression model was used for analysis of repeated measures of salt intake. Results Mean age and salt intake for study participants at first participation in the survey were 56.5±9.3 years and 12.8±3.3 g/day in men and 55.8±9.4 years and 10.6±2.5 g/day in women, respectively. Mean energy intake decreased in men and women in all age groups from the first to fifth study waves. Eight-year longitudinal data showed that salt intake decreased in men. In stratified analyses by age, mean salt intake in men decreased 0.08 g/year among 40- to 49-year-olds, 0.09 g/year among 50- to 59-year-olds, 0.16 g/year among 60- to 69-year-olds, and 0.14 g/year among 70- to 79-year-olds. For women, mean salt intake decreased 0.08 g/year among 70- to 79-year-olds ( P=0.098). After adjusting for energy intake, salt intake was decreased among 60- to 69-year-old men ( P=0.049) and increased among 50- to 59-year-old women ( P=0.015). Conclusions Absolute salt intake was decreased among all age groups from 40 to 70 years in men and from 70 to 79 years in women. An increased focus on reducing energy intake resulted in only a modest decrease in salt intake. Although we observed a decline, salt intake still exceeded recommended levels. Efforts that focus on salt reduction are needed to address this important public health problem.

Evolution of the epithelial sodium channel and the sodium pump as limiting factors of aldosterone action on sodium transport

Despite large changes in salt intake, the mammalian kidney is able to maintain the extracellular sodium concentration and osmolarity within very narrow margins, thereby controlling blood volume and blood pressure. In the aldosterone-sensitive distal nephron (ASDN), aldosterone tightly controls the activities of epithelial sodium channel (ENaC) and Na,K-ATPase, the two limiting factors in establishing transepithelial sodium transport. It has been proposed that the ENaC/degenerin gene family is restricted to Metazoans, whereas the α- and β-subunits of Na,K-ATPase have homologous genes in prokaryotes. This raises the question of the emergence of osmolarity control. By exploring recent genomic data of diverse organisms, we found that: 1) ENaC/degenerin exists in all of the Metazoans screened, including nonbilaterians and, by extension, was already present in ancestors of Metazoa; 2) ENaC/degenerin is also present in Naegleria gruberi, an eukaryotic microbe, consistent with either a vertical inheritance from the last common ancestor of Eukaryotes or a lateral transfer between Naegleria and Metazoan ancestors; and 3) The Na,K-ATPase β-subunit is restricted to Holozoa, the taxon that includes animals and their closest single-cell relatives. Since the β-subunit of Na,K-ATPase plays a key role in targeting the α-subunit to the plasma membrane and has an additional function in the formation of cell junctions, we propose that the emergence of Na,K-ATPase, together with ENaC/degenerin, is linked to the development of multicellularity in the Metazoan kingdom. The establishment of multicellularity and the associated extracellular compartment ("internal milieu") precedes the emergence of other key elements of the aldosterone signaling pathway.

Role of CYP2C9 genetic variants for salt sensitivity and the regulation of the renin–angiotensin–aldosterone system in normotensive men

Cytochrome P450 (CYP) 2C9 gene polymorphisms have been implicated in regulation of the renin-angiotensin-aldosterone system (RAAS) and salt sensitivity in hypertensive patients. We tested the relevance of CYP2C9 genotypes for regulation of plasma renin activity (PRA), plasma aldosterone concentrations and blood pressure (BP) in response to changes in salt intake in normotensive individuals. Three hundred and ten normotensive men (mean age 24.9 ± 0.1) were studied after a standardized low = 20 mmol/day or high = 220 mmol/day sodium intake for 7 days. Individuals were classified as salt sensitive when the mean arterial BP was more than 3 mmHg higher after high compared with low-salt exposure. CYP2C9*2 and CYP2C9*3 alleles were not associated with salt-sensitivity status or BP phenotypes; CYP2C9*2 had no effect on PRA or plasma aldosterone. CYP2C9*3 carriers showed a significantly lower PRA compared with CYP2C9*1/*1 individuals in the overall study cohort (high salt: 0.39 ± 0.05 vs. 0.62 ± 0.04 ng/ml per h, P = 0.009; low salt: 2.19 ± 0.27 vs. 2.87 ± 0.13 ng/ml per h, P = 0.013). Salt-sensitive CYP2C9*3 carriers exhibited the lowest PRA values and significantly lower 24 h sodium excretion rates during high-salt intake (P = 0.005 vs. CYP2C9*1/*1). Lower plasma aldosterone concentrations were only observed in salt-resistant CYP2C9*3 carriers under low salt (P = 0.039). The present study confirms an association between CYP2C9 polymorphism and activity of the RAAS. Specifically, we detected an overall effect of CYP2C9*3 on lower PRA, but not on salt-sensitive BP regulation in normotensive men. Further studies are needed to analyze the long-term effects of CYP2C9*3 for salt sensitivity and hypertensive diseases.

Nocturnal dipping behaviour in normotensive white children and young adults in response to changes in salt intake

Nocturnal nondipping is a feature of salt-sensitive, hypertensive individuals. In normotensive children and adults, the impact of salt intake on circadian blood pressure (BP) rhythm is not well defined. To test whether a high-salt diet abolishes nocturnal dipping in salt-sensitive, normotensive individuals. In normotensive, healthy individuals dichotomized for age (children: n = 28, age 11.9 +/- 0.8 years, 43% girls; adults: n = 41, age 25.7 +/- 0.9 years, 46% women), 24-h ambulatory BP monitoring was performed and 24-h urine collections were obtained during the steady-state phase of a low and a high-salt diet. Salt-sensitivity was defined as at least 3-mmHg increase in 24-h mean arterial pressure during the high-salt diet. Salt-sensitive children and young adults (n = 11 in each group) and salt-resistant individuals (n = 17 children and n = 30 adults) were recruited. Circadian BP rhythm was maintained irrespective of age, salt intake and salt sensitivity. In contrast to the pronounced pressure response to high salt, a low-salt diet lowered the BP of salt-sensitive individuals as compared with salt-resistant individuals at daytime (SBP 107.6 +/- 1.2 vs. 114.8 +/- 1.6 mmHg, P = 0.002 in adults and SBP/DBP 103.1 +/- 1.6/68.6 +/- 1.5 vs. 111.2 +/- 1.3/74.5 +/- 1.1 mmHg, P = 0.005 in children), yet left night-time BP unchanged. Nonlinear mixed effects modelling indicated a steeper downward slope of BP from daytime to night-time in salt-sensitive as compared with salt-resistant children and all adults (P < 0.0015). Without exception, daytime mean arterial pressure disclosed salt-sensitive individuals upon salt loading. Normotensive children and young adults maintain normal nocturnal BP dipping irrespective of salt intake and of individual salt sensitivity. Thus, daytime BP assessment is sufficient to characterize salt responsiveness in normotensive individuals.

Effects of the peroxisome proliferator-activated receptor (PPAR)-γ agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension. In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45 mg daily during 6 weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension. Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the blood-pressure response to salt and abolished salt sensitivity in salt-sensitive individuals. Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones. ClinicalTrial.gov NCT01090752 Hypertension Research Foundation Lausanne.

Adenosine 2A Receptors and Epoxyeicosatrienoic Acids

Adenosine _2A Receptors and Epoxyeicosatrienoic Acids

Sex dependent differences in collecting duct renin during high salt intake

Collecting duct (CD) renin is upregulated during Ang II‐dependent hypertension. In this study we examined if CD renin exhibits sex differences during changes in salt intake in 19 Sprague‐Dawley rats distributed in 4 groups [1) Controls male (n=5); 2) Controls female (n=5); HS male (n=5); and HS female (n=4) fed a normal and HS diet (8% NaCl). Baseline systolic blood pressure (SBP) was not different between males and female rats (males: 116±3 vs. female: 119±2 mmHg) nor after 2‐weeks fed a HS diet (male 126±2 vs. female: 128±2 mmHg). Although renin mRNA and protein levels examined by qRT‐PCR and Western blot in renal medullary tissues were similar in male and female rats under control conditions [Controls male: mRNA= 1.0±0.4 AU; protein=1.0±0.1 DU vs. Controls female: mRNA=0.3±0.1AU; protein=0.8±0.1 DU)]; HS diet intake significantly increased the CD renin transcript and protein levels in females but not in male rats [mRNA=(HS male: 1.5±0.1 vs. HS female: 3.4±0.6 AU); protein= (HS male: 1.0±0.3 DU vs. HS female: 1.8 ±0.7 DU). These data suggest that although there is not sex difference in CD renin gene expression under basal conditions, HS intake appears to stimulate renin in distal nephron segment only in female rats. Future studies are planned to determine whether HS intake during chronic Ang II infusion leads to sexual dimorphisms of blood pressure during Ang II‐dependent hypertension.

Aplicación práctica de la evaluación de la sensibilidad a la sal

Abundant evidence from epidemiological and experimental studies has established a link between salt and blood pressure values. Individuals have different grades of susceptibility to the pressure effect of salt, a phenomenon known as salt sensitivity. The phenomenon of increase or no change in BP blood pressure values when changing from a low-salt diet to a high-salt diet has resulted in a concept called salt sensitivity or resistance. Salt sensitivity increases with age, black race, diabetes mellitus and renal diseases. A variety of different techniques have been used to assess blood pressure response to changes in salt intake in humans. However, due to the complexity of the procedure they are mainly used for research and occasionally for clinical practice.

Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin–angiotensin system

A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy. On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin–angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy. Blood pressure, heart rate, fetuses and dams' body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin–angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1–7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the LS group than in the NS and HS groups. The PRA was greater in LS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of angiotensins I and II were lower in the HS group than in the NS and LS groups. Placental angiotensin receptor type 1 (AT 1) gene expression and levels of thiobarbituric acid reactive substances (TBARS) were higher in HS dams, as were uterine blood flow and cardiac output. The degree of salt intake did not influence plasma sodium, potassium or creatinine. Although fractional sodium excretion was higher in HS dams than in NS and LS dams, fractional potassium excretion was unchanged. In conclusion, findings from this study indicate that the reduction in fetal weight in response to salt restriction during pregnancy does not involve alterations in uterine-placental perfusion or the RAS. Moreover, no change in fetal weight is observed in response to salt overload during pregnancy. However, salt overload did lead to an increase in placental weight and uterine blood flow associated with alterations in maternal plasma and placental RAS. Therefore, these findings indicate that changes in salt intake during pregnancy lead to alterations in uterine-placental perfusion and fetal growth.

Low salt intake increases adenosine type 1 receptor expression and function in the rat proximal tubule

Adenosine mediates Na+ reabsorption in the proximal tubule (PT) and other segments by activating adenosine type 1 receptors (A1-AR). We tested the hypothesis that A1-AR in the PT is regulated by salt intake and participates in the kidney adaptation to changes in salt intake. Absolute fluid reabsorption (Jv) was measured by direct in vivo microperfusion and recollection in rats maintained on low (LS; 0.03% Na, wt/wt)-, normal (NS; 0.3% Na)-, and high-salt (HS; 3.0% Na) diets for 1 wk. The effect of microperfusion of BG9719 a highly selective inhibitor of A1-ARs or adenosine deaminase (AD), which metabolizes adenosine, was measured in each group. Jv was higher in PT from LS rats (LA: 2.8 +/- 0.2 vs. NS: 2.1 +/- 0.2 nl.min(-1).mm(-1), P < 0.001). Jv in HS rats was not different from NS. BG9719 reduced Jv in LS rats by 66 +/- 6% (LS: 2.8 +/- 0.2 vs LS+CVT: 1.3 +/- 0.3 nl.min(-1).mm(-1), P < 0.001), which was greater than its effect in NS (45 +/- 4%) or HS (41 +/- 4%) rats. AD reduced Jv similarly, suggesting that A1-ARs are activated by local production of adenosine. Expression of A1-AR mRNA and protein was higher (P < 0.01) in microdissected PTs in LS rats compared with NS and HS. We conclude that A1-ARs in the PT are increased by low salt intake and that A1-AR participates in the increased PT reabsorption of solute and fluid in response to low salt intake.