Renal sodium handling in acute and chronic salt loading/depletion protocols: the confounding influence of acute water loading.

OBJECTIVES: Renal tubular sodium handling was measured in healthy subjects submitted to acute and chronic salt-repletion/salt-depletion protocols. The goal was to compare the changes in proximal and distal sodium handling induced by the two procedures using the lithium clearance technique. METHODS: In nine subjects, acute salt loading was obtained with a 2 h infusion of isotonic saline, and salt depletion was induced with a low-salt diet and furosemide. In the chronic protocol, 15 subjects randomly received a low-, a regular- and a high-sodium diet for 1 week. In both protocols, renal and systemic haemodynamics and urinary electrolyte excretion were measured after an acute water load. In the chronic study, sodium handling was also determined, based on 12 h day- and night-time urine collections. RESULTS: The acute and chronic protocols induced comparable changes in sodium excretion, renal haemodynamics and hormonal responses. Yet, the relative contribution of the proximal and distal nephrons to sodium excretion in response to salt loading and depletion differed in the two protocols. Acutely, subjects appeared to regulate sodium balance mainly by the distal nephron, with little contribution of the proximal tubule. In contrast, in the chronic protocol, changes in sodium reabsorption could be measured both in the proximal and distal nephrons. Acute water loading was an important confounding factor which increased sodium excretion by reducing proximal sodium reabsorption. This interference of water was particularly marked in salt-depleted subjects. CONCLUSION: Acute and chronic salt loading/salt depletion protocols investigate different renal mechanisms of control of sodium balance. The endogenous lithium clearance technique is a reliable method to assess proximal sodium reabsorption in humans. However, to investigate sodium handling in diseases such as hypertension, lithium should be measured preferably on 24 h or overnight urine collections to avoid the confounding influence of water.

Réduction de la consommation de sel: opportunité, impact et stratégies. [Population reduction of salt consumption: opportunities, impact and strategies].

A national survey showed that Swiss people eat high quantity of salt (9.1 g per day on average). The Swiss Federal Office of Public Health (FOPH) has launched a strategy to reduce salt intake in the population in order to decrease cardiovascular morbidity and mortality, mainly via blood pressure reduction. The most effective public health measures are to reduce the salt content of processed food rich in salt because they do not need to change consumers' eating behaviours. The FOPH has chosen to collaborate with the food industry on a voluntary basis. Regular population-based surveys will be needed to monitor the impact of current measures on salt consumption, hypertension prevalence as well as cardiovascular morbidity and mortality in the years to come.

Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency.

Hyperammonemic disorders in pediatric patients lead to poorly understood irreversible effects on the developing brain that may be life-threatening. We showed previously that some of these NH4+-induced irreversible effects might be due to impairment of axonal growth that can be protected under ammonium exposure by creatine co-treatment. The aim of the present work was thus to analyse how the genes of arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), allowing creatine synthesis, as well as of the creatine transporter SLC6A8, allowing creatine uptake into cells, are regulated in rat brain cells under NH4+ exposure. Reaggregated brain cell three-dimensional cultures exposed to NH4Cl were used as an experimental model of hyperammonemia in the developing central nervous system (CNS). We show here that NH4+ exposure differentially alters AGAT, GAMT and SLC6A8 regulation, in terms of both gene expression and protein activity, in a cell type-specific manner. In particular, we demonstrate that NH4+ exposure decreases both creatine and its synthesis intermediate, guanidinoacetate, in brain cells, probably through the inhibition of AGAT enzymatic activity. Our work also suggests that oligodendrocytes are major actors in the brain in terms of creatine synthesis, trafficking and uptake, which might be affected by hyperammonemia. Finally, we show that NH4+ exposure induces SLC6A8 in astrocytes. This suggests that hyperammonemia increases blood-brain barrier permeability for creatine. This is normally limited due to the absence of SLC6A8 from the astrocyte feet lining microcapillary endothelial cells, and thus creatine supplementation may protect the developing CNS of hyperammonemic patients.

Impact de la consommation de sel sur la santé: les croyances de la population suisse [Impact of salt intake on health: beliefs of the Swiss population].

Excessive salt intake increases the risk of developing hypertension and cardiovascular disease. Sodium intake remains high both in developed and emerging countries. The Swiss Federal Office of Public Health has ordered a national survey on the salt intake in Switzerland, realized in different centers. This article presents the results of the awareness of the Swiss population concerning the relationship between excessive salt intake and health. This survey reveals a lack of knowledge regarding the association between high salt intake and cardiovascular disease, the sodium content of usual food, and the recommended daily value of sodium intake. Strategies to reduce salt consumption need to be reinforced by collaborations between health authorities and health care professionals.

Salt subtraction in patients on maintenance hemodialysis. Efficacy and limitations.

In 6 hypertensive patients with terminal renal failure maintained on hemodialysis, the effects of 'salt subtraction' and of sequential ultrafiltrating were evaluated. Following each of 3 weekly hemodialysis sessions, salt subtraction was carried out by ultrafiltrating 1 liter and simultaneously infusing an equal volume of 5% dextrose. This resulted in a net sodium loss without hypovolemia. After a 2-week period of this procedure, the blood pressure prior to dialysis was lower (156/76 +/- 12/5 mm Hg) than after a comparable number of sequential ultrafiltration sessions (181/88 +/- 10/6 mm Hg; mean +/- SEM). This difference was not statistically significant. At the same time, body weight was comparable at 64.4 +/- 3 and 64.7 +/- 4 kg, respectively. Neither plasma renin activity nor plasma catecholamines responded with a clear increase to either procedure. The limited effect on blood pressure and the renin system of a marked sodium removal during salt subtraction suggests that sodium must still be present in excess in these patients. The procedure of salt subtraction appears safe and subjectively well tolerated, but it can probably not be used as the sole means of decreasing total body sodium without associating dietary measures to reduce sodium intake.

Renal effects of selective cyclooxygenase-2 inhibition in normotensive salt-depleted subjects.

PURPOSE: To compare the renal hemodynamic and tubular effects of celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) to those of naproxen, a nonselective inhibitor of cyclooxygenases in salt-depleted subjects. METHODS AND SUBJECTS: Forty subjects were randomized into four parallel groups to receive 200 mg celecoxib twice a day, 400 mg celecoxib twice a day, 500 mg naproxen twice a day, or a placebo for 7 days according to a double-blind study design. Blood pressure, renal hemodynamics, and urinary water and electrolyte excretion were measured before and for 3 hours after drug intake on days 1 and 7. RESULTS: Celecoxib had no effect on systemic blood pressure, but short-term transient decreases in renal blood flow and glomerular filtration rate were found with the highest dose of 400 mg on day 1. On the first day, both celecoxib and naproxen decreased urine output (P < .05) and sodium, lithium, and potassium excretion (P < .01). On day 7, similar effects on water and sodium excretion were observed. During repeated administration, a significant sodium retention occurred during the first 3 days. CONCLUSION: In salt-depleted subjects, selective inhibition of COX-2 causes sodium and potassium retention. This suggests that an increased selectivity for COX-2 does not spare the kidney, at least during salt depletion.

Inducible kidney-specific Sgk1 knockout mice show a salt-losing phenotype.

The expression of the serum- and glucocorticoid-regulated kinase 1 (Sgk1) is induced by mineralocorticoids and, in turn, upregulates the renal epithelial Na(+) channel (ENaC). Total inactivation of Sgk1 has been associated with transient urinary Na(+) wasting with a low-Na(+) diet, while the aldosterone-mediated ENaC channel activation was unchanged in the collecting duct. Since Sgk1 is ubiquitously expressed, we aimed to study the role of renal Sgk1 and generated an inducible kidney-specific knockout (KO) mouse. We took advantage of the previously described TetOn/CreLoxP system, in which rtTA is under the control of the Pax8 promotor, allowing inducible inactivation of the floxed Sgk1 allele in the renal tubules (Sgk1fl/fl/Pax8/LC1 mice). We found that under a standard Na(+) diet, renal water and Na(+)/K(+) excretion had a tendency to be higher in doxycycline-treated Sgk1 KO mice compared with control mice. The impaired ability of Sgk1 KO mice to retain Na(+) increased significantly with a low-salt diet despite higher plasma aldosterone levels. On a low-Na(+) diet, the Sgk1 KO mice were also hyperkaliuric and lost body weight. This phenotype was accompanied by a decrease in systolic and diastolic blood pressure. At the protein level, we observed a reduction in phosphorylation of the ubiquitin protein-ligase Nedd4-2 and a decrease in the expression of the Na(+)-Cl(-)-cotransporter (NCC) and to a lesser extent of ENaC.

Obtenció d'estruvita a partir de la fracció líquida digerida de purins de vaca

Actualment a Catalunya existeixen zones amb importants limitacions per l’aplicació de purins al sòl, pel que és imprescindible trobar alternatives de gestió i tractament que permetin l’aprofitament adequat dels recursos continguts a les dejeccions ramaderes sense afectar el medi. La digestió anaeròbia és una de les tècniques utilitzades en el tractament de les dejeccions ramaderes. L’efluent líquid que s’obté d’aquest tractament no modifica el contingut de nitrogen i fòsfor i per tant ha de ser gestionat correctament. L’objectiu general d’aquest projecte és avaluar la precipitació d’estruvita (sal de magnesi, amoni i fosfat) com una alternativa de gestió de l’efluent líquid d’una planta de digestió anaeròbia i compostatge que tracta dejeccions ramaderes conjuntament amb altres residus orgànics. S’han avaluat els efectes dels diferents paràmetres operacionals en la formació d’estruvita (pH, temperatura, velocitat d’agitació, alcalinitat), mitjançant assaigs en discontinu amb solució sintètica. A continuació s’ha procedit a obtenir estruvita a partir de la fracció líquida digerida de purí (FLD), en assaigs en discontinu per estudiar l’efecte del contingut de matèria orgànica i sòlids Totals (ST), així com el contingut en fosfats i el pH de reacció. Finalment, s’han optimitzat els paràmetres de procés en continu, mitjançant la posada en marxa d’un reactor a escala de laboratori i estudi de l’efecte de la velocitat d’agitació i de la introducció del stripping de CO2, tant amb solució sintètica com amb la fracció líquida digerida del purí. Dels resultats obtinguts es pot concloure que els factors que tenen una major influència en el procés d’obtenció d’estruvita són el pH (el pH òptim es situa al voltant de 9), i la presència de matèria orgànica i sòlids ens suspensió, que interfereix de forma quantitativa i qualitativa en la formació de l’estruvita. En el procés en continu s’ha aconseguit reduccions d’un 84% i 98% d’amoni i fòsfor respectivament, obtenintse estruvita que pot ser utilitzada com a fertilitzant d’alliberació lenta. Es pot concloure que la precipitació d’estruvita és una bona alternativa per millorar la gestió de les dejeccions ramaderes alhora que permet recuperar nutrients i tancar cicles. La combinació amb un tractament previ que elimini la matèria orgànica, com podria ser la digestió anaeròbia, i una separació de fases, per eliminar els sòlids en suspensió, es presenta com una configuració amb molts avantatges.

Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2.

Nedd4-2 has been proposed to play a critical role in regulating epithelial Na+ channel (ENaC) activity. Biochemical and overexpression experiments suggest that Nedd4-2 binds to the PY motifs of ENaC subunits via its WW domains, ubiquitinates them, and decreases their expression on the apical membrane. Phosphorylation of Nedd4-2 (for example by Sgk1) may regulate its binding to ENaC, and thus ENaC ubiquitination. These results suggest that the interaction between Nedd4-2 and ENaC may play a crucial role in Na+ homeostasis and blood pressure (BP) regulation. To test these predictions in vivo, we generated Nedd4-2 null mice. The knockout mice had higher BP on a normal diet and a further increase in BP when on a high-salt diet. The hypertension was probably mediated by ENaC overactivity because 1) Nedd4-2 null mice had higher expression levels of all three ENaC subunits in kidney, but not of other Na+ transporters; 2) the downregulation of ENaC function in colon was impaired; and 3) NaCl-sensitive hypertension was substantially reduced in the presence of amiloride, a specific inhibitor of ENaC. Nedd4-2 null mice on a chronic high-salt diet showed cardiac hypertrophy and markedly depressed cardiac function. Overall, our results demonstrate that in vivo Nedd4-2 is a critical regulator of ENaC activity and BP. The absence of this gene is sufficient to produce salt-sensitive hypertension. This model provides an opportunity to further investigate mechanisms and consequences of this common disorder.

Nutrition in cardiovascular disease: salt in hypertension and heart failure.

There is much evidence for a causal relationship between salt intake and blood pressure (BP). The current salt intake in many countries is between 9 and 12 g/day. A reduction in salt intake to the recommended level of 5-6 g/day lowers BP in both hypertensive and normotensive individuals. A further reduction to 3-4 g/day has a much greater effect. Prospective studies and outcome trials have demonstrated that a lower salt intake is associated with a decreased risk of cardiovascular disease. Increasing evidence also suggests that a high salt intake is directly related to left ventricular hypertrophy (LVH) independent of BP. Both raised BP and LVH are important risk factors for heart failure. It is therefore possible that a lower salt intake could prevent the development of heart failure. In patients who already have heart failure, a high salt intake aggravates the retention of salt and water, thereby exacerbating heart failure symptoms and progression of the disease. A lower salt intake plays an important role in the management of heart failure. Despite this, currently there is no clear evidence on how far salt intake should be reduced in heart failure. Our personal view is that these patients should reduce their salt intake to <5 g/day, i.e. the maximum intake recommended by the World Health Organisation for all adults. If salt intake is successfully reduced, there may well be a need for a reduction in diuretic dosage.

Nitrate and ammonium in soil solution in tobacco management systems

Tobacco farmers of southern Brazil use high levels of fertilizers, without considering soil and environmental attributes, posing great risk to water resources degradation. The objective of this study was to monitor nitrate and ammonium concentrations in the soil solution of an Entisol in and below the root zone of tobacco under conventional tillage (CT), minimum tillage (MT) and no-tillage (NT). The study was conducted in the small-watershed Arroio Lino, in Agudo, State of Rio Grande do Sul, Brazil. A base fertilization of 850 kg ha-1 of 10-18-24 and topdressing of 400 kg ha-1 of 14-0-14 NPK fertilizer were applied. The soil solution was sampled during the crop cycle with a tension lysimeter equipped with a porous ceramic cup. Ammonium and nitrate concentrations were analyzed by the distillation and titration method. Nitrate concentrations, ranging from 8 to 226 mg L-1, were highest after initial fertilization and decreased during the crop cycle. The average nitrate (N-NO3-) concentration in the root zone was 75 in NT, 95 in MT, and 49 mg L-1 in CT. Below the root zone, the average nitrate concentration was 58 under NT, 108 under MT and 36 mg L-1 under CT. The nitrate and ammonium concentrations did not differ significantly in the management systems. However, the nitrate concentrations measured represent a contamination risk to groundwater of the watershed. The ammonium concentration (N-NH4+) decreased over time in all management systems, possibly as a result of the nitrification process and root uptake of part of the ammonium by the growing plants.

Ammonium chloride as nitrogen source in sugarcane harvested without burning

The great difficulty of incorporation of N fertilizers into the "green sugarcane" system causes concern and since urea is the most commonly used source, there is the risk of loosing NH3 through volatilization. For this reason, a field experiment was undertaken (in a Hapludox Typic) with the objective of evaluating the agronomic efficiency of ammonium chloride on stubble of the second ratoon (SP89 1115), as well as its residual effect on the subsequent cycle (third ratoon). The experimental design was randomized blocks with four replications. Treatments consisted of three N rates (60, 120 and 180 kg ha-1 N) in the form of NH4Cl, in addition to a control treatment without the addition of N fertilizer. The ratoon cane of the second cutting was harvested in November 2006 and the treatments were applied in December 2006. The second ratoon was harvested mechanically in November 2007 and in December 2007, 450 kg ha-1 of the NPK mixture 20-05-19 was applied, providing 90, 22 and 86 kg ha-1 N, P2O5 and K2O, respectively, for the purpose of evaluating the effect of residual-N from the treatments implanted in December 2006. An increase in the rates of N-NH4Cl had a positive effect on the leaf concentrations of P, Mg and S. Stalk yield (MSS - Mg ha-1 of sugarcane stalks) and sugar (MSH - Mg ha-1 of sucrose) in the November 2006 harvest responded linearly to the increase of N doses in the form of NH4Cl. In relation to the effect of residual-N in the 2007/2008 harvest, it was observed, in general, that the concentrations of macronutrients in the sugarcane leaf +1 were within the range considered adequate in the state of São Paulo, Brazil. The residual-N of the NH4Cl doses resulted in a significant reduction in stalk (MSS) and sugar (MSH) production. It may be concluded that the NH4Cl source at a dose of 120 kg ha-1 N in ratoon fertilization of the second cutting was agronomically efficient, presenting, however, less efficiency of residual-N in the subsequent cycle.

Dynamics of ammonium and pH in the solution of soils with different salinity levels, growing irrigated rice

Rice in Rio Grande do Sul State is grown mostly under flooding, which induces a series of chemical, physical and biological changes in the root environment. These changes, combined with the presence of rice plants, affect the availability of exchangeable ammonium (NH4+) and pH of soil solution, whereas the dynamics of both variables can be influenced by soil salinity, a common problem in the coastal region. This study was conducted to evaluate the dynamics of exchangeable NH4+ and pH in the soil solution, and their relation in the solution of Albaqualf soils with different salinity levels, under rice. Four field experiments were conducted with soils with exchangeable Na percentage (ESP) of 5.6, 9.0, 21.2, and 32.7 %. Prior to flooding, soil solution collectors were installed at depths of 5, 10 and 20 cm. The soil solution was collected weekly, from 7 to 91 days after flooding (DAF), to analyze exchangeable NH4+ and pH in the samples. Plant tissue was sampled 77 DAF, to determine N uptake and estimate the contribution of other N forms to rice nutrition. The content of exchangeable NH4+ decreased over time at all sites and depths, with a more pronounced reduction in soils with lower salinity levels, reaching values close to zero. A possible contribution of non-exchangeable NH4+ forms and N from soil organic matter to rice nutrition was observed. Soil pH decreased with time in soils with ESP 5.6 and 9.0 %, being positively correlated with the decreasing NH4+ levels at these sites.

Salt content labelling of foods in supermarkets in Finland

Selostus: Suolamerkinnät valintamyymälöiden pakatuissa elintarvikkeissa