NaCl Intake Research Articles

The lateral parabrachial nucleus and central angiotensinergic mechanisms in the control of sodium intake induced by different stimuli

Angiotensin II (ANG II) is a typical facilitatory stimulus for sodium appetite. Surprisingly, hyperosmolarity and central cholinergic stimulation, two classical antinatriorexigenic stimuli, also facilitate NaCl intake when they are combined with injections of the α2-adrenoceptor/imidazoline agonist moxonidine into the lateral parabrachial nucleus (LPBN). In the present study, we tested the relative importance of central angiotensinergic and cholinergic mechanisms for the control of water and NaCl intake by combining different dipsogenic or natriorexigenic stimuli with moxonidine injection into the LPBN. Adult male Holtzman rats (n=9–10/group) with stainless steel cannulas implanted in the lateral ventricle and LPBN were used. Bilateral injections of moxonidine (0.5 nmol) into the LPBN increased water and 0.3M NaCl intake in rats that received furosemide+captopril injected subcutaneously, ANG II (50ng) or carbachol (cholinergic agonist, 4 nmol) injected intracerebroventricularly (icv) or 2M NaCl infused intragastrically (2ml/rat). Losartan (AT1 antagonist, 100μg) or atropine (muscarinic antagonist, 20 nmol) injected icv abolished the effects on water and 0.3M NaCl of moxonidine combined to either 2M NaCl intragastrically or carbachol icv. However, atropine icv did not change 0.3M NaCl intake produced by direct central action of ANG II like that induced by ANG II icv or furosemide+captopril combined with moxonidine into the LPBN. The results suggest that different stimuli, including hyperosmolarity and central cholinergic stimulation, share central angiotensinergic activation as a common mechanism to facilitate sodium intake, particularly when they are combined with deactivation of the LPBN inhibitory mechanisms.

Sodium chloride promotes tissue inflammation via osmotic stimuli in subtotal-nephrectomized mice

Chronic inflammation, which is often associated with high all-cause and cardiovascular mortality, is prevalent in patients with renal failure; however, the precise mechanisms remain unclear. High-salt intake was reported to induce lymphangiogenesis and autoimmune diseases via osmotic stimuli with accumulation of sodium or chloride. In addition, sodium was recently reported to be stored in the extremities of dialysis patients. We studied the effects and mechanisms of high salt loading on tissue and systemic inflammation in subtotal-nephrectomized mice (5/6Nx) and in cultured cells. Macrophage infiltration in the peritoneal wall (P<0.001), heart (P<0.05) and para-aortic tissues (P<0.001) was significantly higher in 5/6Nx with salt loading (5/6Nx/NaCl) than in 5/6Nx without salt loading (5/6Nx/Water); however, there were no significant differences in blood pressure and renal function between the groups. Tissue interleukin-6, monocyte chemotactic protein-1 (MCP-1), serum- and glucocorticoid-inducible kinase 1 (Sgk1) and tonicity-responsive enhancer binding protein (TonEBP) mRNA were significantly elevated in the peritoneal wall and heart with 5/6Nx/NaCl when compared with 5/6Nx/Water. Sodium was stored in the abdominal wall, exerting high-osmotic conditions. Reversal of salt loading reduced macrophage infiltration associated with decreased TonEBP in 5/6Nx/NaCl. Macrophage infiltration associated with fibrosis induced by salt loading was decreased in the 5/6Nx/NaCl/CC chemokine receptor 2 (CCR2, receptor of MCP-1)-deficient mice when compared with 5/6Nx/NaCl/Wild mice, suggesting that CCR2 is required for macrophage infiltration in 5/6Nx with NaCl loading. In cultured mesothelial cells and cardiomyocytes, culture media with high NaCl concentration induced MCP-1, Sgk1 and TonEBP mRNA, all of which were suppressed by TonEBP siRNA, indicating that both MCP-1 and Sgk1 are downstream of TonEBP. Our study indicates that high NaCl intake induces MCP-1 expression leading to macrophage infiltration via the TonEBP-MCP-1 pathway in 5/6Nx/NaCl mice, and that TonEBP has a central role in inflammation in patients with renal failure taking high salt.

Thick Ascending Limb‐derived TNF production regulates the blood pressure response to high NaCl intake

We previously showed that the thick ascending limb (TAL) produces tumor necrosis factor‐alpha (TNF) in response to diverse stimuli and acts as an endogenous inhibitor of NKCC2 expression and activity. In this study we determined the effect of TNF derived from the TAL on the renal adaptation to high NaCl (HS) intake. TNF levels were higher in urine (40±4 vs 18±5 pg/24 h) of mice that ingested 1% NaCl in the drinking water for three days compared with tap water. The increase in urinary TNF levels was associated with a 4‐four fold increase (p&lt;0.05) in TNF mRNA abundance in mTAL tubules isolated from mice given HS. In contrast, plasma levels of TNF remained unchanged in these mice (HS: 20±3 vs tap water: 18±3pg/ml). The increase in renal TNF mRNA levels induced by HS intake decreased by more than 80% (p&lt;0.05) in mice given an intrarenal injection of a lentivirus construct that silences TNF in the kidney. Neither injection of a control lentivirus (U6) nor EGFP‐TNF‐ex4 altered baseline blood pressure in mice ingesting a normal salt diet and tap water. However, renal‐specific silencing of TNF rapidly increased blood pressure in mice drinking 1% NaCl (U6: 110±4 vs shTNF: 136±6mmHg; p&lt;0.05), an effect that was sustained for 11 days. Baseline blood pressure was rapidly restored when mice were switched to tap water (days 12–16), and rapidly increased when they were switched back to HS (days 17–21). Renal outer medullary NKCC2A mRNA accumulation increased approximately 3‐fold (p&lt;0.05) after injection of EGFP‐TNF‐ex4 followed by ingestion of HS for 3 days compared with U6 control groups. The Cre/loxP recombination system was then used to generate TAL‐specific TNF knockout mice (TAL‐TNF KO). Specific recombination in the TAL was validated by PCR of microdissected nephron segments. The recombined allele product (0.45kb) was present in TAL tubules but not PT, IMCD, or spleen. Baseline blood pressure was similar in TNF‐TAL KO mice and littermate controls but increased when TNF‐TAL KO mice were given HS for three days. Food, water intake, and body weight were not different between groups in either model of TNF deletion and the increases in blood pressure were not associated with damage to glomeruli, blood vessels, or tubules. The increase in renal TNF levels in response to HS intake without a concomitant increase in blood pressure or an inflammatory component, and the increase in blood pressure in response to HS when TNF is silenced in the TAL suggests deficiency of TAL‐derived TNF is sufficient to render normotensive healthy mice salt‐sensitive.

Rapid stimulation of sodium intake combining aldosterone into the 4th ventricle and the blockade of the lateral parabrachial nucleus

Chronic infusion of aldosterone into the 4th ventricle (4th V) induces robust daily sodium intake, whereas acute injection of aldosterone into the 4th V produces no sodium intake. The inhibitory mechanism of the lateral parabrachial nucleus (LPBN) restrains sodium intake induced by different natriorexigenic stimuli and might affect the acute response to aldosterone into the 4th V. In the present study, 1.8% NaCl and water intake was tested in rats treated with acute injections of aldosterone into the 4th V combined with the blockade of the inhibitory mechanisms with injections of moxonidine (α2 adrenergic/imidazoline agonist) or methysergide (a serotonergic antagonist) into the LPBN. Male Holtzman rats with stainless steel cannulas implanted in the 4th V and bilaterally in the LPBN were used. Aldosterone (250 or 500ng) into the 4th V combined with vehicle into the LPBN induced no 1.8% NaClintake compared to control (1.5±1.1 and 1.1±0.4, respectively, vs. vehicle into 4th V: 1.0±0.5ml/2h). However, aldosterone (250 or 500ng) into the 4th V combined with moxonidine (0.5nmol) into the LPBN induced strong ingestion of 1.8% NaCl (12.7±4.6 and 17.6±3.7ml/2h, respectively). Aldosterone (250ng) into the 4th V combined with methysergide (4μg) into the LPBN also induced 1.8% NaCl intake (17.6±5.4ml/2h). These data suggest that the inhibitory mechanisms of the LPBN counteract the facilitation of sodium intake produced by aldosterone injected into the 4th, restraining sodium intake in this condition.

Long-Term High Salt Intake Involves Reduced SK Currents and Increased Excitability of PVN Neurons with Projections to the Rostral Ventrolateral Medulla in Rats.

Evidence indicates that high salt (HS) intake activates presympathetic paraventricular nucleus (PVN) neurons, which contributes to sympathoexcitation of salt-sensitive hypertension. The present study determined whether 5 weeks of HS (2% NaCl) intake alters the small conductance Ca2+-activated potassium channel (SK) current in presympathetic PVN neurons and whether this change affects the neuronal excitability. In whole-cell voltage-clamp recordings, HS-treated rats had significantly decreased SK currents compared to rats with normal salt (NS, 0.4% NaCl) intake in PVN neurons. The sensitivity of PVN neuronal excitability in response to current injections was greater in HS group compared to NS controls. The SK channel blocker apamin augmented the neuronal excitability in both groups but had less effect on the sensitivity of the neuronal excitability in HS group compared to NS controls. In the HS group, the interspike interval (ISI) was significantly shorter than that in NS controls. Apamin significantly shortened the ISI in NS controls but had less effect in the HS group. This data suggests that HS intake reduces SK currents, which contributes to increased PVN neuronal excitability at least in part through a decrease in spike frequency adaptation and may be a precursor to the development of salt-sensitive hypertension.

Aldosterone induces rapid sodium intake by a nongenomic mechanism in the nucleus tractus solitarius.

The purpose of this study was to determine whether aldosterone has a rapid action in the nucleus tractus solitarius (NTS) that increases sodium intake, and to examine whether this effect of aldosterone, if present, is mediated by G protein-coupled estrogen receptor (GPER). Adult male Sprague-Dawley rats with a stainless-steel cannula in the NTS were used. Aldosterone was injected into the NTS at the doses of 1, 5, 10 and 20 ng 0.1 μl−1. A rapid dose-related increase of 0.3 M NaCl intake was induced within 30 min and this increase was not suppressed by the mineralocorticoid receptor (MR) antagonist spironolactone (10 ng 0.1 μl−1). Water intake was not affected by aldosterone. The GPER agonist G-1 produced a parallel and significant increase in sodium intake, while pre-treatment with GPER antagonist G15 (10 ng 0.1 μl−1) blocked the G-1 or aldosterone-induced rapid sodium intake. In addition, sodium intake induced by sodium depletion or low-sodium diet fell within 30 min after injection into the NTS of the MR antagonist spironolactone, while G15 had no effect. Our results confirm previous reports, and support the hypothesis that aldosterone evokes rapid sodium intake through a non-genomic mechanism involving GPER in NTS.

Fourth ventricle injection of ghrelin decreases angiotensin II-induced fluid intake and neuronal activation in the paraventricular nucleus of the hypothalamus

Ghrelin acts in the CNS to decrease fluid intake under a variety of dipsogenic and natriorexigenic conditions. Previous studies on this topic, however, focused on the forebrain as a site of action for this effect of ghrelin. Because the hindbrain contains neural substrates that are capable of mediating the well-established orexigenic effects of ghrelin, the current study tested the hypothesis that ghrelin applied to the hindbrain also would affect fluid intake. To this end, water and saline intakes were stimulated by central injection of angiotensin II (AngII) in rats that also received injections of ghrelin (0.5μg/μl) into either the lateral or fourth ventricle. Ghrelin injected into either ventricle reduced both water and 1.8% NaCl intake that was stimulated by AngII. The nature of the intake effect revealed some differences between the injection sites. For example, forebrain application of ghrelin reduced saline intake by a reduction in both the number of licking bursts and the size of each licking burst, but hindbrain application of ghrelin had a more selective effect on burst number. In an attempt to elucidate a brain structure in which hindbrain-administered ghrelin and forebrain-administered AngII interact to cause the ingestive response, we used Fos-immunohistochemistry in rats given the treatments used in the behavioral experiments. Although several brain areas were found to respond to either ghrelin or AngII, of the sites examined, only the paraventricular nucleus of the hypothalamus (PVN) emerged as a potential site of interaction. Specifically, AngII treatment caused expression of Fos in the PVN that was attenuated by concomitant treatment with ghrelin. These experiments provide the novel finding that the hindbrain contains elements that can respond to ghrelin and cause decreases in AngII-induced fluid intake, and that direct actions by ghrelin on forebrain structures is not necessary. Moreover, these studies suggest that the PVN is an important site of interaction between these two peptides.

Abstract 102: Role of Renal Tubular NHE3 for Blood Pressure and Salt Homeostasis

The Na + /H + exchanger isoform 3 (NHE3) is expressed in the intestine and the kidney where it facilitates Na + absorption and H + secretion. The importance of NHE3 in the kidney for NaCl homeostasis and blood pressure regulation, relative to the intestine, is not known. To investigate this, we examined kidney-specific NHE3 knockout mice (NHE3 loxloxPax8Cre ) and control mice (Con, NHE3 loxlox ) under normal, low or high dietary NaCl intake. Under normal dietary NaCl intake, no significant differences were detected between genotypes in body weight, fluid or food intake, blood pH and plasma Na + , K + or aldosterone levels. However, urinary pH was significantly elevated in NHE3 loxloxPax8Cre mice and GFR was significantly lower (457±20 vs 358±17 μl/min, P&lt;0.05). High NaCl intake (4% for 10 days) had no impact on plasma Na + in Con mice; but plasma Na + concentrations in NHE3 loxloxPax8Cre mice were susceptible to the effects of low NaCl (&lt;0.01% for 10 days) (-3.9±1.0 mM, P&lt;0.05) or high NaCl intake (+2.2±0.6 mM, P&lt;0.05) compared to baseline conditions. Low NaCl diet decreased plasma K + levels in Con mice (-0.5±0.2 mM, P&lt;0.05) but to a significantly greater amount in NHE3 loxloxPax8Cre mice (-1.2±0.1 mM, P&lt;0.05). Plasma aldosterone was not significantly different between Con and NHE3 loxloxPax8Cre mice under low (345±96 vs 498±78 pg/ml) or high NaCl intake (60±19 vs 86±20 pg/ml). Low NaCl intake decreased GFR in Con (-110±13 μl/min, P&lt;0.05) and NHE3 loxloxPax8Cre (-99±8 μl/min, P&lt;0.05) mice, whereas high NaCl intake was without effect on GFR in either genotype. Dietary NaCl did not affect blood pressure in Con mice (low NaCl: 102±3; high NaCl: 102±3 mmHg); however, blood pressure was significantly lower in NHE3 loxloxPax8Cre mice and salt-sensitive (low NaCl: 81±2; high NaCl: 91±2 mmHg, P&lt;0.05). Alterations in the abundances of several Na + transport proteins within the kidney tubule system were also apparent in NHE3 loxloxCre mice under different dietary conditions. In conclusion, renal NHE3 is required to maintain blood pressure and steady state plasma Na + levels when dietary NaCl intake is modified.

Lateral parabrachial nucleus and opioid mechanisms of the central nucleus of the amygdala in the control of sodium intake

Facilitatory and inhibitory mechanisms in the central nucleus of the amygdala (CeA) and the lateral parabrachial nucleus (LPBN), respectively, are important for the control of sodium and water intake. Here we investigated the importance of the opioid mechanisms in the CeA for water and 0.3M NaCl intake in euhydrated or hyperosmotic rats treated with injections of muscimol (GABAA agonist) or moxonidine (α2 adrenergic/imidazoline agonist) into the LPBN, respectively. Male Holtzman rats (n=4–8/group) with stainless steel cannulas implanted bilaterally in the CeA and in the LPBN were used. The ingestion of 0.3M NaCl and water by euhydrated rats treated with muscimol (0.5nmol/0.2μl) into the LPBN (29.4±2.7 and 15.0±2.4ml/4h, respectively) was abolished by the previous injections of naloxone (opioid antagonist, 40μg/0.2μl) into the CeA (0.7±0.3 and 0.3±0.1ml/4h, respectively). The ingestion of 0.3M NaCl by rats treated with intragastric 2M NaCl (2ml/rat) combined with moxonidine (0.5nmol/0.2μl) into the LPBN (17.0±3.8ml/2h) was also strongly reduced by the previous injections of naloxone into the CeA (3.2±2.5ml/2h). Sucrose intake was not affected by naloxone injections into the CeA, which minimized the possibility of non-specific inhibition of ingestive behaviors with this treatment. The present results suggest that opioid mechanisms in the CeA are essential for hypertonic NaCl intake when the LPBN inhibitory mechanisms are deactivated or attenuated with injections of muscimol or moxonidine in this area.

Significant natriuretic and antihypertensive action of the epithelial sodium channel blocker amiloride in diabetic patients with and without nephropathy.

Diabetic nephropathy is associated with aberrant glomerular filtration of serine proteases. The study was designed to test the hypothesis that the epithelial sodium channel is activated proteolytically by urine plasmin in diabetic nephropathy and mediates renal sodium retention. In an open-label intervention study on type 1 diabetes patients on standardized NaCl intake (200 mmol/day) with (n = 15) and without diabetic nephropathy (control, n = 12), urinary Na excretion in response to oral amiloride (20 or 40 mg/day for 2 days) was compared. A total of 27 patients completed the study and nine diabetic nephropathy and eight control study participants were compliant (24-h urine Na excretion of 200 mmol ± 30%). Amiloride increased significantly total and fractional Na excretion in both groups. Total natriuresis and weight loss were significantly larger in the control group compared with diabetic nephropathy at day 1 of amiloride, whereas fractional Na excretion did not differ. Amiloride intervention increased plasma renin concentration only in diabetic nephropathy group; it reduced SBP in both groups, whereas DBP was reduced in diabetic nephropathy group only. Albuminuria was reduced significantly by amiloride in diabetic nephropathy group. Urine total amiloride concentration was not different between groups (12 ± 1 and 16 ± 1 μmol/l, respectively). Urine total plasminogen and active plasmin were reduced after amiloride in diabetic nephropathy. Amiloride increased renal Na excretion, reduced blood pressure, albuminuria, and total and active plasmin in urine. It is concluded that epithelial sodium channel is an attractive target to attain blood pressure control in long-term type I diabetes with no enhanced activity associated with nephropathy.

Short-term cross-sensitizion of need-free sugar intake by combining sodium depletion and hypertonic NaCl intake

History of sodium depletion cross-sensitizes the effects of drugs of abuse. The objective of the present study was to find out if history of sodium depletion also cross-sensitizes a natural reward such as sugar intake in the rat. Sodium depletion was induced by furosemide combined with removal of ambient sodium for 24 h; it was repeated seven days later. The depletion was immediately followed by 0.3 M NaCl intake in a sodium appetite test (active sodium repletion). Seven days after the last depletion, hydrated and fed (need-free) sucrose-naïve animals were offered 10% sucrose in a first 2-h sucrose test. The sucrose test was repeated once a day in a series of five consecutive days. History of sodium depletion enhanced sucrose intake in the first and second tests; it had no effect from the third to fifth sucrose test. The effect on the initial sucrose intake tests disappeared if the rats did not ingest 0.3 M NaCl in the sodium appetite test. Prior experience with sucrose intake in need-free conditions had no effect on sodium appetite. History of intracellular dehydration transiently influenced sucrose intake in the first sucrose test. We found no evidence for thirst sensitization. We conclude that history of dehydration, particularly that resulting from sodium depletion, combined to active sodium repletion, produced short-term cross-sensitization of sucrose intake in sucrose-naïve rats. The results suggest that the cross-sensitization of sucrose intake related with acquisition of sugar as a novel nutrient rather than production of lasting effects on sugar rewarding properties.

Textural improvement of salt-reduced Alaska pollack (Theragra chalcogramma) roe product by CaCl2

Salt-reduced Alaska pollack roe benefits public health by decreasing NaCl intake; however, it has a poor texture with low breaking strength. This study addresses the feasibility of NaCl reduction in salted roe products, with focusing on the improvement of breaking strength using CaCl2. Salted roe products were prepared by immersing Alaska pollack roe in either NaCl solutions (3.5, 7.0, 15.0, 20.0, and 25.0%) or 7.0% NaCl solutions with added CaCl2 (0.0, 0.5, 1.0, 2.0, and 3.0%). Breaking strength, moisture and salt contents, eggshell protein composition of the salted roe products, as well as total endogenous transglutaminase (TGase) activity in various NaCl and CaCl2 concentrations were analyzed. CaCl2 addition enhanced eggshell protein crosslinking and breaking strength of the salt-reduced roe products. An acyl transfer reaction catalyzed by calcium-dependent TGase may be responsible for the eggshell protein crosslinking and improved texture. Thus, we successfully developed a salt-reduced Alaska roe product using CaCl2.

Importance of the lateral parabrachial nucleus to sodium balance in fluid-depleted rats

The lateral parabrachial nucleus (LPBN) exerts an important inhibitory influence for the control of sodium and water intake. However, the importance of LPBN on renal responses and cardiovascular changes during extracellular dehydration are still unknown. Here we investigated the effects of bilateral injections of moxonidine (alpha2-adrenergic and imidazoline receptor agonist) on renal and cardiovascular changes in fluid-depleted rats. Male Wistar rats (n=4–8 per group) with bilateral stainless steel guide-cannulas implanted into the LPBN were treated with subcutaneous furosemide (10mg/kg)+captopril (5mg/kg) to induce fluid depletion. Forty-five min later vehicle or moxonidine (0.5nmol/0.2μl) were bilaterally injected into the LPBN. In fluid-depleted rats, moxonidine produced strong 0.3M NaCl and water intake without noticeable changes in cardiovascular parameters. Moxonidine did not change sodium excretion (488±135, vs. vehicle: 376±75μEq/1h) or urinary volume (2.5±0.7, vs. vehicle: 2.5±0.3ml/1h) in fluid-depleted rats without access to fluids for rehydration. However, moxonidine decreased natriuresis (462±127, vs. vehicle: 888±122μEq/1h) and diuresis (2.5±0.5, vs. vehicle: 4.5±0.5ml/1h) in fluid-depleted rats submitted to i.g. rehydration. These data suggest that alpha2-adrenergic mechanism of the LPBN facilitates sodium/water retention and body fluid volume expansion during extracellular dehydration.

Gastrorenal Axis.

Gastrorenal Axis.

Putrescine production by Lactococcus lactis subsp. cremoris CECT 8666 is reduced by NaCl via a decrease in bacterial growth and the repression of the genes involved in putrescine production

The reduction of NaCl in food is a public health priority; high NaCl intakes have been associated with serious health problems. However, it is reported that reducing the NaCl content of cheeses may lead to an increase in the content of biogenic amines (BAs). The present work examines the effect of NaCl on the accumulation of putrescine (one of the BAs often detected at high concentration in cheese) in experimental Cabrales-like cheeses containing Lactococcus lactis subsp. cremoris CECT 8666, a dairy strain that catabolises agmatine to putrescine via the agmatine deiminase (AGDI) pathway. The genes responsible for this pathway are grouped in the AGDI cluster. This comprises a regulatory gene (aguR) (transcribed independently), followed by the catabolic genes that together form an operon (aguBDAC). Reducing the NaCl concentration of the cheese led to increased putrescine accumulation. In contrast, increasing the NaCl concentration of both pH-uncontrolled and pH-controlled (pH 6) cultures of L. lactis subsp. cremoris CECT 8666 significantly inhibited its growth and the production of putrescine. Such production appeared to be inhibited via a reduction in the transcription of the aguBDAC operon; no effect on the transcription of aguR was recorded. The present results suggest that low-sodium cheeses are at risk of accumulating higher concentrations of putrescine.

Quantifying The Contributions Of Sodium And Calcium In Bone Using Serial Dxa Scans

Bone has been hypothesized to serve as a sodium reservoir to buffer acute and chronic derangements in plasma sodium concentration ([Na+]). However, the contributions of sodium in bone have yet to be quantified in imaging studies. PURPOSE: To: 1) quantify the contributions of 6g sodium chloride (NaCl) on bone mineral content (BMC) and density (BMD) using dual energy x-ray absorptiometry (DXA) scans; 2) compare the contributions of 6g NaCl vs. 6g calcium citrate (Ca3Cit2) on both BMC and BMD; and 3) assess whole body BMC changes in humans 2hrs after oral ingestion of 6g NaCl. METHODS: 1) Ten DXA scans serially performed on a spine phantom (alone) and then with 6g NaCl placed over the spine as: solid 1g tablets; crushed tablets in 1.5mL Eppendorfs (tubes); and as a solution in tubes. 2) Ten DXA scans performed on a spine phantom plus 6g Ca3Cit2 as solid 1g tablets and as crushed tablets in tubes. 3) 14 healthy humans ingested 6g NaCl, (6x1g tablets) with DXA scans taken immediately after ingestion (+tablets; just swallowed) and then repeated 2hrs following oral tablet ingestion (-tablets; due to GI absorption). RESULTS: Mean spine phantom BMC (51.38±0.26g;CV=0.51%) was significantly lower compared with spine phantom plus: NaCl tablets (55.39±0.23;p<0.0001); NaCl tubes (54.87±0.26g;p<0.0001); NaCl solution (52.49±0.28g;p<0.0001); Ca3Cit2 tablets (55.05±0.31g;p<0.0001); and Ca3Cit2 tubes (53.68±0.39g;p<0.0001). Mean spine phantom BMD (0.989±0.004g/cm2;CV=0.50%) was statistically lower when compared with phantom plus: NaCl tablets (1.063g/cm2±0.005;p<0.0001); NaCl tubes (1.056±0.005g/cm2;p<0.0001); NaCl solution (1.006±0.005g/cm2;p<0.0001); Ca3Cit2 tablets (1.058±0.006g/cm2;p<0.0001); and Ca3Cit2 tubes (1.021±0.005g/cm2;p<0.0001). Absorption of 6gm NaCl tablets into the bloodstream 2hrs after oral ingestion reduced whole body BMC by -5.5±27g. CONCLUSIONS: 6g NaCl caused significant increases in BMC and BMD in DXA scans when placed over a spine phantom in: tablet form, when crushed in tubes; and dissolved in solution. Increases in BMC and BMD were similar between 6g NaCl and 6g Ca3Cit2. Alternatively, GI absorption of 6g NaCl tablets after oral ingestion resulted in a ~6g decrease in total body BMC. Thus, changes in BMC and BMD may reflect Na+ and Ca++ mobilization in DXA scan measurements.

Taste and Hypertension in Humans: Targeting Cardiovascular Disease.

The association between salty taste and NaCl intake with hypertension is well-established, although it is far from completely understood. Other taste types such as sweet, umami or bitter have also been related to alterations in blood pressure. Here, we review the mutual relationship between taste and hypertension to identify potential avenues to better control blood pressure. This review focuses on published data involving humans, with the exception of a section on molecular mechanisms. There is compelling evidence to suggest that changes in salty taste sensitivity can be used to predict the onset of hypertension. This goes hand in hand with the medical concept of sodium sensitivity, which also increases with age, particularly in hypertensive patients. The association of hypertension with the loss of taste acuity less definitive with some data/conclusions masked by the use of anti-hypertensive drugs. In fact, this group of therapeutic agents can reduce food taste perception resulting in mild to severe hypogeusia and dysgeusia. In the elderly, antihypertensive drugs may lead to a loss of appetite, thus, selecting treatments with low or no impact on taste perception should be advised. Pharmacological approaches to mitigate cardiovascular disease (CVD) could well take a different spin in the future following the discovery of taste receptors (TAS1R and TAS2R) in the cardiovascular system. Finally, long-term dietary strategies to minimize the risk of development of hypertension and CVD are discussed identifying several nutrients and public health policies with relevant potential.

Serotonin release in the subfornical organ area induced by sodium and water intake in the rat

Previous studies have shown that the subfornical organ (SFO) is involved in the modulation of sodium intake in rats. To clarify whether serotonergic mechanisms in the SFO participate in the modulatory system, the present study was carried out to examine the effects of sodium and water intake on serotonin (5-hydroxytryptamine, 5-HT) release in the subfornical organ (SFO) in freely moving rats. The ingestion of 0.3M NaCl and water was induced by subcutaneous injections of the diuretic furosemide (FURO, 10mg/kg) and the angiotensin converting enzyme inhibitor captopril (CAP, 5mg/kg), and extracellular concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the region of the SFO were measured using intracerebral microdialysis techniques. The combined treatment with FURO and CAP elicited significant decreases in the 5-HT and 5-HIAA levels in the SFO area. The 0.3M NaCl and water intake caused by the treatment significantly enhanced the 5-HT and 5-HIAA concentrations in the SFO area compared with the basal levels. No significant changes in the 5-HT and 5-HIAA levels caused by either the FURO and CAP treatment or water and NaCl intake were observed in the sites away from the SFO. These results suggest that the serotonergic mechanism in the SFO may be important for the control of sodium appetite and thirst.

Crystallization of NaCl by fast evaporation of water in droplets of NaCl solutions

Excessive salt (NaCl) intake has been related to several diseases. Small salt crystals that rapidly dissolve in the oral cavity may decrease swallowing of untasted salt. The aim of this research was to evaluate the crystallization of salt as microcrystals by fast water evaporation from droplets of saline solutions within a hot oil phase. The effects of the oil temperature (150; 165 and 180°C), droplet volume (17 and 42μL) and brine concentration (15 and 26% w/v) were studied. Crystalline particles with mean sizes between 9 and 23μm, and containing about 2% of remaining oil were obtained. The crystal size decreased by increasing the oil temperature, solution concentration and volume of the droplets. The dissolution rate of these microcrystals was more than 2 times faster than that of the original crystals. The microcrystals obtained could be added in surface-salted foods (snacks, salads) to optimize or reduce the sodium intake while maintaining saltiness perception.

High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

Aims: To examine the effects of 2 weeks of high-NaCl diet on left ventricular (LV) morphology and serum levels of cardiac troponin T (cTnT) in rats with adenine-induced chronic renal failure (ACRF). Methods: Male Sprague-Dawley rats either received chow containing adenine or were pair-fed an identical diet without adenine [controls (C)]. Approximately 10 weeks after the beginning of the study, the rats were randomized to either remain on a normal NaCl diet (NNa; 0.6%) or to be switched to high-NaCl chow (HNa; 4%) for 2 weeks, after which acute experiments were performed. Results: Rats with ACRF showed statistically significant increases (p < 0.001) in arterial pressure (AP), LV weight and fibrosis, and serum cTnT levels compared to controls. Two weeks of high-NaCl intake augmented the increases in AP, LV weight and fibrosis, and serum cTnT concentrations only in ACRF rats (p < 0.05 for group × NaCl intake interaction). Compared to group C-NNa, cTnT levels were elevated approximately 6-fold in group ACRF-NNa and 24-fold in group ACRF-HNa. Focal LV injury with cardiomyocyte necrosis, scarring, and fibrinoid necrosis of small arteries were only detected in group ACRF-HNa. There was a strong correlation between the degree of LV fibrosis and serum cTnT levels in ACRF rats (r = 0.81, p < 0.01). Conclusion: Two weeks of high-NaCl diet in rats with ACRF produces LV injury and aggravates increases in serum cTnT levels, presumably by causing hypertension-induced small artery lesions leading to myocardial ischemia. This model may be suitable for studying pathophysiological mechanisms in chronic renicardiac syndromes.