Salt Deprivation Research Articles

Postprandial sodium sensing by enteric neurons in Drosophila.

Sodium is essential for all living organisms1. Animals including insects and mammals detect sodium primarily through peripheral taste cells2-7. It is not known, however, whether animals can detect this essential micronutrient independently of the taste system. Here, we report that Drosophila Ir76b mutants that were unable to detect sodium2 became capable of responding to sodium following a period of salt deprivation. From a screen for cells required for the deprivation-induced sodium preference, we identified a population of anterior enteric neurons, which we named internal sodium-sensing (INSO) neurons, that are essential for directing a behavioural preference for sodium. Enteric INSO neurons innervate the gut epithelia mainly through their dendritic processes and send their axonal projections along the oesophagus to the brain and to the crop duct. Through calcium imaging and CaLexA experiments, we found that INSO neurons respond immediately and specifically to sodium ions. Notably, the sodium-evoked responses were observed only after a period of sodium deprivation. Taken together, we have identified a taste-independent sodium sensor that is essential for the maintenance of sodium homeostasis.

Non‐random distribution of ungulate salt licks relative to distance from North American oceanic margins

AbstractAimTerrestrial deposition of aerosol marine sodium declines with distance from coastlines. Salt deprivation in vertebrate herbivores and salt‐seeking behaviours should hence increase with distance inland. We analyse published geospatial data on ungulate‐patronized salt licks to test whether they are non‐randomly distributed relative to distance from oceans and elevation.LocationCanada, Alaska and the contiguous United States.TaxonCetartiodactyla (even‐toed ungulates).MethodsWe determined the land area and median elevation of 100 km increments from the North American coast. The null model of the expected number of licks within each interval was determined by the ratio of the interval's land area to the total land area, multiplied by the total number of licks. We asked whether the number of licks further from coastlines was significantly higher than chance. We also assessed whether licks occur disproportionately at higher elevations, comparing the median elevation of observed licks to the median elevation within each interval.ResultsWe found a strong positive relationship between salt lick patronage by ungulates and distance from the coast. Licks occurred significantly less often within, and more often beyond, 500 km inland, and at significantly higher elevations than would be expected by chance.Main conclusionsThese findings indicate that the patronage of salt licks is constrained geographically, and that the foraging behaviour of ungulates and other phytophagous vertebrate taxa may be influenced over large spatial scales by sodium availability. Salt‐seeking behaviour varies on a wide biogeographical scale across North America, with concomitant implications for vertebrate herbivore behaviour and ecology.

Ion‐poor water and dietary salt deprivation upregulate the ghrelinergic system in the goldfish (Carassius auratus)

Because the ghrelinergic system in teleost fishes is broadly expressed in organs that regulate appetite as well as those that contribute to the regulation of salt and water balance, we hypothesized that manipulating salt and water balance in goldfish (Carassius auratus) would modulate the ghrelinergic system. Goldfish were acclimated to either freshwater (FW) or ion-poor FW (IPW) and were fed either a control diet containing 1% NaCl or low-salt diet containing 0.1% NaCl. Endpoints of salt and water balance, i.e., serum Na+ and Cl- levels, muscle moisture content and organ-specific Na+ -K+ -ATPase (NKA) activity, were examined in conjunction with brain, gill and gut mRNA abundance of preproghrelin and its receptor, growth hormone secretagogue receptor (ghs-r). Acclimation of fish to IPW reduced serum osmolality and Cl- levels and elevated kidney NKA activity, while FW fish fed a low NaCl diet exhibited a modest reduction in muscle moisture content but otherwise no apparent osmoregulatory disturbance. In contrast, a combined treatment of IPW acclimation and low dietary NaCl content reduced serum osmolality and Cl- levels, elevated muscle moisture content and increased gill, kidney and intestinal NKA activity. This intensified response to the combined effects of water and dietary ion deprivation is consistent with an increased effort to enhance ion acquisition. In association with these latter observations, a significant upregulation of preproghrelin mRNA expression in brain and gut was observed. A significant increase in ghs-r mRNAs was also observed in the gill of goldfish acclimated to IPW alone but a reduction in dietary NaCl content did not impact the ghrelinergic system of goldfish in FW. The results support the hypothesis that the ghrelinergic system is modulated in response to manipulated salt and water balance. Whether the central and peripheral ghrelinergic system contributes to ionic homeostasis in goldfish currently remains unclear and warrants further research.

Genomic Survey of Salt Acclimation-Related Genes in the Halophilic Cyanobacterium Euhalothece sp. Z-M001

Like other halophilic cyanobacterial genomes, the de novo-assembled genome of Euhalothece sp. Z-M001 lacks genes encoding keto-carotenoid biosynthesis enzymes, despite the presence of genes encoding carotenoid-binding proteins (CBPs). Consistent with this, HPLC analysis of carotenoids identified β-carotene and zeaxanthin as the dominant carotenoids. CBPs coexpressed with the zeaxanthin biosynthesis gene increased the survival rates of Escherichia coli strains by preventing antibiotic-induced accumulation of reactive oxygen species (ROS). RNA-seq analysis of Euhalothece revealed that among various salt resistance-related genes, those encoding the Na+ transporting multiple resistance and pH adaptation (Mrp) systems, glycine betaine biosynthesis enzymes, exopolysaccharide metabolic enzymes, and CBPs were highly upregulated, suggesting their importance in hypersaline habitats. During the early phase of salt deprivation, the amounts of β-carotene and zeaxanthin showed a negative correlation with ROS content. Overall, we propose that in some halophilic cyanobacteria, β-carotene and zeaxanthin, rather than keto-carotenoids, serve as the major chromophores for CBPs, which in turn act as effective antioxidants.

Sox6 as a new modulator of renin expression in the kidney.

Juxtaglomerular (JG) cells, major sources of renin, differentiate from metanephric mesenchymal cells that give rise to JG cells or a subset of smooth muscle cells of the renal afferent arteriole. During periods of dehydration and salt deprivation, renal mesenchymal stromal cells (MSCs) differentiate from JG cells. JG cells undergo expansion and smooth muscle cells redifferentiate to express renin along the afferent arteriole. Gene expression profiling comparing resident renal MSCs with JG cells indicates that the transcription factor Sox6 is highly expressed in JG cells in the adult kidney. In vitro, loss of Sox6 expression reduces differentiation of renal MSCs to renin-producing cells. In vivo, Sox6 expression is upregulated after a low-Na+ diet and furosemide. Importantly, knockout of Sox6 in Ren1d+ cells halts the increase in renin-expressing cells normally seen during a low-Na+ diet and furosemide as well as the typical increase in renin. Furthermore, Sox6 ablation in renin-expressing cells halts the recruitment of smooth muscle cells along the afferent arteriole, which normally express renin under these conditions. These results support a previously undefined role for Sox6 in renin expression.

Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts.

Mass extinctions occur frequently in natural history. While studies of animals that became extinct can be informative, it is the survivors that provide clues for mechanisms of adaptation when conditions are adverse. Here, we describe a survival pathway used by many species as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability. Fructose, whether supplied in the diet (primarily fruits and honey), or endogenously (via activation of the polyol pathway), preferentially shifts the organism towards the storing of fuel (fat, glycogen) that can be used to provide energy and water at a later date. Fructose causes sodium retention and raises blood pressure and likely helped survival in the setting of dehydration or salt deprivation. By shifting energy production from the mitochondria to glycolysis, fructose reduced oxygen demands to aid survival in situations where oxygen availability is low. The actions of fructose are driven in part by vasopressin and the generation of uric acid. Twice in history, mutations occurred during periods of mass extinction that enhanced the activity of fructose to generate fat, with the first being a mutation in vitamin C metabolism during the Cretaceous-Paleogene extinction (65 million years ago) and the second being a mutation in uricase that occurred during the Middle Miocene disruption (12-14 million years ago). Today, the excessive intake of fructose due to the availability of refined sugar and high-fructose corn syrup is driving 'burden of life style' diseases, including obesity, diabetes and high blood pressure.

Blood Pressure Lowering and Safety Improvements With Liver Angiotensinogen Inhibition in Models of Hypertension and Kidney Injury.

Uncontrolled hypertension is an important contributor to cardiovascular disease. Despite the armamentarium of antihypertensive treatments, there remains a need for novel agents effective in individuals who cannot reach acceptable blood pressure levels. Inhibitors targeting the renin-angiotensin-aldosterone system (RAAS) are widely used but may not optimally inhibit RAAS and demonstrate an acceptable safety profile. Experiments were conducted to characterize a series of AGT (angiotensinogen) antisense oligonucleotides (ASOs) and compare their efficacy and tolerability to traditional RAAS blockade. AGT ASOs which target multiple systemic sites of AGT versus an N-acetylgalactosamine-conjugated AGT ASO that targets the liver were compared with captopril and losartan. Spontaneously hypertensive rats fed an 8% NaCl diet, a model of malignant hypertension resistant to standard RAAS inhibitors, demonstrated robust and durable blood pressure reductions with AGT ASO treatments, which was not observed with standard RAAS blockade. Studies in rat models of acute kidney injury produced by salt deprivation revealed kidney injury with ASO treatment that reduced kidney-expressed AGT, but not in animals treated with the N-acetylgalactosamine AGT ASO despite comparable plasma AGT reductions. Administration of either captopril or losartan also produced acute kidney injury during salt deprivation. Thus, intrarenal RAAS derived from kidney AGT, and inhibited by the standard of care, contributes to the maintenance of renal function during severe RAAS challenge. Such improvements in efficacy and tolerability by a liver-selective AGT inhibitor could be desirable in individuals not at their blood pressure goal with existing RAAS blockade.

IMCD to commercialize DuPont's enzymes in Europe and North Africa

Nephron specific regulation of chloride channel CLC-K2 mRNA in the ratThis study investigated the influence of salt intake on the nephron specific gene expression of the kidney chloride channel CLC-K2. To this end, male Sprague-Dawley rats were fed a low (0.02% wt/wt), normal (0.6% wt/wt), or high salt (8% wt/wt) diet for ten days, or they received the loop diuretic furosemide (12 mg/kg/day) for six days.Expression and regulation of messenger RNA for CLC-K2 Was demonstrated by RNase protection assay and in situ hybridization in kidney cortex, outer medulla and inner medulla. Tubular localization and regulation were determined precisely by reverse transcription-polymerase chain reaction (RT-PCR) and real time PCR of microdissected nephron segments.In situ hybridization analysis and RNase protection assay of the total kidney revealed a down-regulation of CLC-K2 mRNA in the high salt diet rats and an up-regulation of CLC-K2 mRNA in furosemide treated rats, which were restricted to the outer medulla. Microdissection of collagenase treated kidney revealed CLC-K2 mRNA expression in the outer medullary thick ascending limb (mTAL), cortical thick ascending limb (cTAL), distal convoluted tubule (DCT), connecting tubule and cortical collecting duct (CNT/CCD), and outer medullary collecting duct (OMCD), whereas no signals were detected in proximal convoluted and straight tubules (PCT and PST), descending thin limb from the outer medulla (dTL), descending and ascending thin limb from the inner medulla (TL), inner medullary collecting duct (IMCD) and glomeruli (glom). Using RT-PCR and real time PCR, the changing levels of CLC-K2 mRNA after furosemide treatment or high salt diet were restricted to the mTAL, whereas CLC-K2 mRNA levels in cTAL and OMCD were not changed in furosemide or high salt rats compared to time paired controls.Given that CLC-K2 expressed in the thick ascending limb of Henle's loop is responsible for net chloride reabsorption in this part of the nephron, our findings suggest that in states of surplus salt and in states of severe salt deprivation, selective regulation of CLC-K2 mRNA plays a role in the adaptation of the kidney to different salt loads.

Aldosterone acutely stimulates NCC activity via a SPAK-mediated pathway

Hypertension is a leading cause of morbidity and mortality worldwide, and disordered sodium balance has long been implicated in its pathogenesis. Aldosterone is perhaps the key regulator of sodium balance and thus blood pressure. The sodium chloride cotransporter (NCC) in the distal convoluted tubule of the kidney is a major site of sodium reabsorption and plays a key role in blood pressure regulation. Chronic exposure to aldosterone increases NCC protein expression and function. However, more acute effects of aldosterone on NCC are unknown. In our salt-abundant modern society where chronic salt deprivation is rare, understanding the acute effects of aldosterone is critical. Here, we examined the acute effects (12-36 h) of aldosterone on NCC in the rodent kidney and in a mouse distal convoluted tubule cell line. Studies demonstrated that aldosterone acutely stimulated NCC activity and phosphorylation without affecting total NCC abundance or surface expression. This effect was dependent upon the presence of the mineralocorticoid receptor and serum- and glucocorticoid-regulated kinase 1 (SGK1). Furthermore, STE20/SPS-1-related proline/alanine-rich kinase (SPAK) phosphorylation also increased, and gene silencing of SPAK eliminated the effect of aldosterone on NCC activity. Aldosterone administration via a minipump in adrenalectomized rodents confirmed an increase in NCC phosphorylation without a change in NCC total protein. These data indicate that acute aldosterone-induced SPAK-dependent phosphorylation of NCC increases individual transporter activity.

Loss of renal medullary endothelin B receptor function during salt deprivation is regulated by angiotensin II

We have recently demonstrated that chronic infusion of exogenous ANG II, which induces blood pressure elevation, attenuates renal medullary endothelin B (ET(B)) receptor function in rats. Moreover, this was associated with a reduction of ET(B) receptor expression in the renal inner medulla. The aim of this present work was to investigate the effect of a physiological increase in endogenous ANG II (low-salt diet) on the renal ET system, including ET(B) receptor function. We hypothesized that endogenous ANG II reduces renal medullary ET(B) receptor function during low-salt intake. Rats were placed on a low-salt diet (0.01-0.02% NaCl) for 2 wk to allow an increase in endogenous ANG II. In rats on normal-salt chow, the stimulation of renal medullary ET(B) receptor by ET(B) receptor agonist sarafotoxin 6c (S6c) causes an increase in water (3.6 ± 0.4 from baseline vs. 10.5 ± 1.3 μl/min following S6c infusion; P < 0.05) and sodium excretion (0.38 ± 0.06 vs. 1.23 ± 0.17 μmol/min; P < 0.05). The low-salt diet reduced the ET(B)-dependent diuresis (4.5 ± 0.5 vs. 6.1 ± 0.9 μl/min) and natriuresis (0.40 ± 0.11 vs. 0.46 ± 0.12 μmol/min) in response to acute intramedullary infusion of S6c. Chronic treatment with candesartan restored renal medullary ET(B) receptor function; urine flow was 7.1 ± 0.9 vs. 15.9 ± 1.7 μl/min (P < 0.05), and sodium excretion was 0.4 ± 0.1 vs. 1.1 ± 0.1 μmol/min (P < 0.05) before and after intramedullary S6c infusion, respectively. Receptor binding assays determined that the sodium-depleted diet resulted in a similar level of ET(B) receptor binding in renal inner medulla compared with rats on a normal-salt diet. Candesartan reduced renal inner medullary ET(B) receptor binding (1,414 ± 95 vs. 862 ± 50 fmol/mg; P < 0.05). We conclude that endogenous ANG II attenuates renal medullary ET(B) receptor function to conserve sodium during salt deprivation independently of receptor expression.

Appetitive changes during salt deprivation are paralleled by widespread neuronal adaptations in nucleus accumbens, lateral hypothalamus, and central amygdala

Salt appetite is a goal-directed behavior in which salt-deprived animals ingest high salt concentrations that they otherwise find aversive. Because forebrain areas such as the lateral hypothalamus (LH), central amygdala (CeA), and nucleus accumbens (NAc) are known to play an important role in this behavior, we recorded from these areas while water-deprived (WD) and salt-deprived (SD) rats performed a two-bottle choice test between 0.5 M salt (NaCl) and 0.4 M sucrose. In the SD state, the preference ratio for high molar salt markedly increased. Electrophysiological recordings analyzed with respect to the onset of licking clusters revealed the presence of both excitatory and inhibitory neuronal responses during salt and/or sucrose consumption. In the NAc, putative medium spiny neurons and tonically active neurons exhibited excitatory and inhibitory responses. In all areas, compared with those recorded during the WD state, neurons recorded during the SD state showed an increase in the percentage of salt-evoked excitatory responses and a decrease in the percentage of sucrose-evoked inhibitory responses, suggesting that a subset of the neuronal population in these areas codes for the increased motivational and/or hedonic value of the salt solution. In addition, in the SD state, the firing of excitatory neurons in LH and CeA became more synchronized, indicating a greater functional connectivity between salt-responsive neurons in these areas. We propose that plastic changes in the feeding-related neuronal populations of these forebrain areas arise when changes in metabolic state alter the hedonic and motivational value of a particular taste stimulus.

Les ARN non-codants impliqués dans la réponse des plantes aux contraintes environnementales

In recent years, in addition to mRNAs, the non-protein-coding RNAs (or ncRNAs) have emerged as a major part of the eukaryotic transcriptome. New genomic approaches allowed the discovery of many novel long and small ncRNAs that may be linked to the generation of evolutionary complexity in multicellular organisms. Many long ncRNAs are regulated by abiotic stresses although only very few long ncRNAs have been functionally analyzed. On the other hand, small RNAs act in the regulation of gene expression at transcriptional or post-transcriptional level and several among them have been linked to abiotic stress responses. Here we describe various ncRNAs associated with environmental stress responses such as to salt, cold or nutrient deprivation. The understanding of these RNA networks may reveal novel mechanisms involved in plant adaptation to changing environmental conditions.

Should we now abandon the low-salt diet?

The publication in the May 2011 issue of JAMA of the paper by Stolarz-Skrzypek et al .1 once again raises previous opinions that low-salt diet in normal people can be harmful. The conclusions of that paper,1 that low-salt diet is associated with increased mortality has been heavily criticized in the US press, and the Lancet ,2 and has been impressively rebutted by the leader of the research team.3 Interestingly, in the same study,1 there was no increased mortality in those with high salt intake. The JAMA study1 was large; 3681 subjects, normal European Caucasians, daily urinary sodium excretion rates were measured as an indication of sodium intake, as recommended by He and MacGregor4 (excess sodium is excreted in the urine5). We can expect protracted debate on the rights and wrongs, for and against the ‘salt causes hypertension’ hypothesis. The issue that should be considered now is: Is there evidence to suggest that salt deprivation causes harm? The recommendation to the general public to restrict its sodium intake [mainly as ‘salt’—sodium chloride (the terms salt and sodium are often used synonymously. However, on a weight basis, salt comprises 40% sodium and 60% chloride. 1 g salt = 0.4 g sodium; 100 MEq = 2.9 g sodium = 5.8 g salt/sodium chloride = 100 mmol)] is based on a large body of opinion. Official bodies such as NICE6 and the Institute of Medicine7 repeat this recommendation in press releases, which do not include the evidence on which the advice is based and do not mention the contrary evidence. In an extreme form this is expressed as ‘a reduction in population salt intake worldwide will result in a major improvement in public health’,4 based on the fact that arterial blood pressure (BP) can be reduced in normals and hypertensives by salt restriction. The coronary …

Complex challenges–what will the collecting duct do when both Na+ and K+ have to be conserved

the aldosterone-sensitive distal nephron, comprising the distal convoluted tubule (DCT), connecting tubule (CNT), cortical collecting duct (CCD), and outer medullary collecting duct, plays a major role in controlling Na+ and K+ homeostasis. A key mechanism, characterized mostly in the CCD, involves

Replacement of connexin 40 by connexin 45 causes ectopic localization of renin-producing cells in the kidney but maintains in vivo control of renin gene expression

Deletion of connexin 40 (Cx40) leads to ectopic hyperplasia of renin-producing cells in the kidney, which is associated with dysregulated hyperreninemia and hypertension. The aim of this study was to determine whether Cx45 is able to substitute the function of Cx40 with regard to the localization of renin-producing cells. For this purpose, we have studied the distribution of renin-expressing cells under both normal conditions and during a stimulatory challenge of the renin system by inducing salt deprivation in mice, achieved by replacing the coding sequence of the Cx40 gene with that of Cx45 (Cx40ki45). In both wild-type (WT) mice and Cx40ki45 mice under normal conditions, renin-expressing cells were located at the juxtaglomerular position, whereas in Cx40-deficient mice they were located in the periglomerular interstitium. Upon challenge of the renin system, renin mRNA and the number of renin-expressing cells increased in WT mice in the media layer of afferent arterioles, while neither parameter changed significantly in Cx40-deficient mice. In Cx40ki45 mice, challenge of the renin system markedly increased both renin mRNA and the number of renin-expressing cells. However, the newly recruited renin-expressing cells were localized mainly outside the afferent vessels in the periglomerular interstitium. We found no evidence of cell divisions in renin-expressing cells in any of the genotypes investigated in this study, suggesting that the ectopically localized, renin-expressing cells in Cx40ki45 mice were already preexisting but were not renin-expressing under normal conditions. In summary, we infer from our findings that the function of Cx40 for the localization of potential renin-producing cells cannot be substituted by that of Cx45, although the regulability of renin gene expression can.

Connexin Expression in Renin-Producing Cells

Absence of connexin 40 (Cx40) leads to ectopic juxtaglomerular renin expression and abrogates recruitment of renin-expressing cells in the adult kidney but does not disturb renin expression during kidney development. To find an explanation for these observations, we aimed to analyze the expression pattern of major vascular Cxs in normal juxtaglomerular epithelioid cells, in recruited renin-expressing cells, and in fetal renin-expressing cells. We found that during kidney development, the appearance of renin-producing cells paralleled the expression of Cx40 and, to a lesser extent, Cx45 but not other Cxs. In the adult kidney, juxtaglomerular epithelioid cells expressed Cx40 and lesser amounts of Cx37 and Cx43 but not Cx45, which localized to arteriolar smooth muscle cells. Recruitment of renin-producing cells in adult kidneys in response to long-term salt deprivation of mice correlated with the reappearance of only Cx40. Cx40-null renin-producing cells did not express Cx37, Cx43, or Cx45. These findings suggest that Cx40 expression is a characteristic of renin-producing cells in the kidney, and it seems to be essential in the recruitment of renin-producing cells in the adult but not the fetal kidney.

Compensatory role for Sgk2 mediated sodium reabsorption during salt deprivation in Sgk1 knockout mice

Compensatory role for Sgk2 mediated sodium reabsorption during salt deprivation in Sgk1 knockout mice

Mobilization of osmotically inactive Na+ by growth and by dietary salt restriction in rats

The idea that an osmotically inactive Na(+) storage pool exists that can be varied to accommodate states of Na(+) retention and/or Na(+) loss is controversial. We speculated that considerable amounts of osmotically inactive Na(+) are lost with growth and that additional dietary salt excess or salt deficit alters the polyanionic character of extracellular glycosaminoglycans in osmotically inactive Na(+) reservoirs. Six-week-old Sprague-Dawley rats were fed low-salt (0.1%; LS) or high-salt (8%; HS) diets for 1 or 4 wk. At their death, we separated the tissues and determined their Na(+), K(+), and water content. Three weeks of growth reduced the total body Na(+) content relative to dry weight (rTBNa(+)) by 23%. This "growth-programmed" Na(+) loss originated from the bone and the completely skinned and bone-removed carcasses. The Na(+) loss was osmotically inactive (45-50%) or osmotically active (50-55%). In rats aged 10 wk, compared with HS, 4 wk of LS reduced rTBNa(+) by 9%. This dietary-induced Na(+) loss was osmotically inactive ( approximately 50%) and originated largely from the skin, while approximately 50% was osmotically active. LS for 1 wk did not reduce skin Na(+) content. The mobilization of osmotically inactive skin Na(+) with long-term salt deprivation was associated with decreased negatively charged skin glycosaminoglycan content and thereby a decreased water-free Na(+) binding capacity in the extracellular matrix. Our data not only serve to explain discrepant results in salt balance studies but also show that glycosaminoglycans may provide an actively regulated interstitial cation exchange mechanism that participates in volume and blood pressure homeostasis.

Roles of learning and motivation in preference behavior: Mediation by entorhinal cortex, dorsal and ventral hippocampus

In the latent cue preference (LCP) task, water-deprived rats alternately drink a salt solution in one distinctive compartment of a conditioned cue preference (CCP) apparatus and water in the other compartment over 8 days (training trials). They are then given a choice between the two compartments with no solutions present (preference test). Previous findings showed that this training procedure results in two parallel forms of learning: conditioning to water-paired cues (a water-CCP) and latent learning of an association between salt and salt-paired compartment cues (a salt-LCP). Experiment 1 examined these two types of learning in isolation. Results showed that expression of the salt-LCP required salt deprivation during testing, but expression of the water-CCP did not require a deprivation state during testing. Other results showed that salt-LCP learning itself involves two distinct components: (1) the latent association among neutral cues in the salt-paired compartment, and (2) motivational information about salt deprivation during testing. Previous findings also demonstrated roles for the dorsal hippocampus (DH), ventral hippocampus (VH), and entorhinal cortex (EC) in salt-LCP learning. Experiment 2 examined the involvement of these structures during acquisition or expression of salt-LCP learning. Rats with cannulas aimed at DH, VH, or EC were given infusions of muscimol, either before exposure to the salt-paired, but not the water-paired, compartment during training or before the preference test. Inactivation of the DH or EC impaired both acquisition and expression of the association between salt and salt-paired compartment cues, while inactivation of the VH disrupted the influence of motivational information about salt deprivation required to express the salt-LCP. These results suggest unique roles for the EC-DH circuit and VH in salt-LCP learning, as well as a functional dissociation between the DH and VH.

Aldosterone—A Hormone of Cardiovascular Adaptation and Maladaptation

Aldosterone stimulates reabsorption of sodium, sustaining blood volume and pressure in the face of salt deprivation or extracellular fluid depletion. The steroid also stimulates excretion of potassium, protecting extracellular fluid from excessive levels of that ion. These two actions are relatively rapid and clearly adaptive when appropriately initiated and terminated, but maladaptive when prolonged or excessive, causing hypertension and electrolyte imbalance. Aldosterone and other mineralocorticoids exert slower, direct effects on cells in the heart, kidneys, and vessels, leading to hypertrophy, fibrosis, and dysfunction contributing to degenerative cardiovascular diseases. The maladaptive actions of aldosterone are exacerbated by sodium chloride, angiotensin, endothelin, and certain growth factors. Damage can be minimized by antagonists of aldosterone receptors, inhibitors of the renin system, depletion of salt, and repletion of potassium and magnesium. Specific inhibitors of fibrosis and hypertrophy, and more effective inhibitors of the renin system should be useful in the future.