Increased Salt Appetite Research Articles

Sex differences in the regulation of salt appetite in Spontaneously Hypertensive Rats after loss of interoceptive input from the kidney

The average American consumes 3,400 mg/day of sodium, 1000mg over the American Heart Association’s recommended maximum daily allowance. Excessive salt intake accelerates the progression of many diseases including hypertension, congestive heart failure, and chronic kidney disease. Reducing sodium intake has beneficial effects on a population level and in at risk patients. In previous studies we have shown that afferent renal nerves are involved in the regulation of sodium intake in DOCA hypertensive rats. Like DOCA hypertensive rats, Spontaneously Hypertensive rats (SHR) are a model with increased salt appetite. Here, we tested the hypothesis that afferent renal nerves regulate sodium intake in SHR. Secondarily, it is well documented that estrogens modulate salt intake. To examine the effect of sex on sodium intake we compared salt-appetite between male and female SHR. Bilateral afferent renal denervation (ARDN) was performed using the periaxonal application of 33mM capsaicin. In sham rats the renal arteries were isolated but not treated. Mean arterial blood pressure (MAP) was assessed using radiotelemetry, with the catheter implanted in the femoral artery. Four groups of rats were studied: male SHR-sham (n=9), female SHR-sham (n=3), male SHR+ARDN (n=8) and female SHR+ARDN (n=4). All rats were given ad libitum access to two bottles, one containing dH2O and the other containing 1.8% NaCl. The bottle position was rotated, and fluid intake was recorded daily for 21-days. ARDN caused a significant reduction in 1.8% intake in female but not male SHR rats (p=0.02, female SHR-sham v female SHR-ARDN, p>0.99 male SHR v male SHR-ARDN). This effect was specific for saline intake, water intake was not altered by ARDN in the female SHR (p=0.3). The female SHR drank more saline than male SHR when normalized to body weight (p=0.04 female SHR-sham v male SHR-sham). MAP was not reduced by ARDN in the male SHR (p=0.39), and ongoing studies are examining MAP in response to ARDN in female SHR. The data presented demonstrate for the first time that ARDN decreases salt appetite in female but not male SHR. We also found that baseline saline intake was higher in female SHR than male SHR. In future studies we will examine the renal mechanisms underlying these sex differences. Together, these data suggest that reduced sodium intake may offer an additional therapeutic benefit of renal denervation in female patients with hypertension and cardiovascular disease. LE is funded by R01HL152166; ACV is funded by FAPESP. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A viewpoint on aldosterone and BMI related brain morphology in relation to treatment outcome in patients with major depression.

An abundance of knowledge has been collected describing the involvement of neuroendocrine parameters in major depression. The hypothalamic-pituitary-adrenocortical (HPA) axis regulating cortisol release has been extensively studied; however, attempts to target the HPA axis pharmacologically to treat major depression have failed. This review focuses on the importance of the adrenocortical stress hormone aldosterone, which is released by adrenocorticotropic hormone and angiotensin, and the mineralocorticoid receptor (MR) in depression. Depressed patients, in particular those with atypical depression, have signs of central hyperactivation of the aldosterone sensitive MR, potentially as a consequence of a reactive aldosterone release induced by low blood pressure and as a result of low sensitivity of peripheral MR. This is reflected in reduced heart rate variability, increased salt appetite and sleep changes in this group of patients. In addition, enlarged brain ventricles, compressed corpus callosum and changes of the choroid plexus are associated with increased aldosterone (in relation to cortisol). Furthermore, subjects with these features often show obesity. These characteristics are related to a worse antidepressant treatment outcome. Alterations in choroid plexus function as a consequence of increased aldosterone levels, autonomic dysregulation, metabolic changes and/or inflammation may be involved. The characterization of this regulatory system is in its early days but may identify new targets for therapeutic interventions.

Salt Appetite, and the Influence of Opioids.

Due to the biological importance of sodium and its relative scarcity within many natural environments, 'salt appetite' has evolved whereby dietary salt is highly sought after and palatable when tasted. In addition to peripheral responses, salt depletion is detected within the brain via circumventricular organs and 11β-hydroxysteroid dehydrogenase type 2 (HSD2) neurons to increase salt appetite. Salt appetite is comprised of two main components. One component is the incentive salience or motivation for salt (i.e. how much salt is 'wanted'). Incentive salience is dynamic and largely depends on internal homeostatic conditions in combination with the detection of relevant cues. It involves the mesolimbic system and structures such as the central amygdala, and opioid signalling within these regions can increase salt intake in rodents. A second key feature is the hedonic palatability of salt (i.e. how much it is 'liked') when it is tasted. After detection on the tongue, gustatory information passes through the brainstem nucleus of the solitary tract and thalamus, before being consciously detected within the gustatory cerebral cortex. The positive or negative hedonic value of this stimulus is also dynamic, and is encoded by a network including the nucleus accumbens, ventral pallidum, and lateral parabrachial nucleus. Opioid signalling within these areas can alter salt intake, and 'liking'. The overconsumption of dietary salt likely contributes to hypertension and associated diseases, and hence further characterising the role played by opioid signalling has important implications for human health.

Cardiovascular Effects of Aldosterone

Background— High plasma aldosterone has deleterious cardiovascular effects that are independent of blood pressure, but the role of the mineralocorticoid receptor remains unclear. Renal pseudohypoaldosteronism type 1 is a rare autosomal-dominant disease caused by NR3C2 loss-of-function mutations, which is characterized by renal salt loss and compensatory high renin and aldo secretion. We aimed to assess the cardiovascular outcomes in adults carrying NR3C2 mutations. Methods and Results— In this case-control study, 39 NR3C2 mutation carriers were compared with sex- and age-paired noncarriers. Patients underwent cardiac and vascular ultrasound, cardiac MRI with gadolinium injection, measurement of pulse wave velocity, extracellular water, 24-hour ambulatory blood pressure, and autonomous nervous system activity. Mutation carriers showed increased aldo and renin plasma levels (4.5- and 1.6-fold, respectively; P <0.0001), together with increased salt appetite (1.8-fold; P =0.002), with normal extracellular water and blood pressure, and no autonomous nervous system activation. Cardiac and vascular parameters were not significantly different between mutation carriers and noncarriers (no left ventricular remodeling or fibrosis, normal left ventricular systolic function, and aorta stiffness). Tissue Doppler showed better diastolic left ventricular function in mutation carriers (e′, P =0.001; E/e′, P =0.003). Mutation carriers had significantly more frequent history of slow body weight recovery at birth, symptomatic hypotension, and miscarriage in women. Conclusions— Despite life-long increase in plasma aldosterone and renin levels, no adverse cardiovascular outcome occurred in pseudohypoaldosteronism type 1, but rather an improved diastolic left ventricular function. This suggests that the cardiovascular consequences of aldosterone excess require full mineralocorticoid receptor signaling. Clinical Trial Registration— http://www.clinicaltrials.gov ; unique identifier: NCT00646828.

Evaluation of salt appetite in brain specific 11β hydroxysteroid dehydrogenase type 2 knockout (11βHSD2−/−) mice

Male brain specific 11βHSD2−/− mice and floxed controls were individually housed in metabolic cages and basal water turnover assessed over 4 days. In separate studies mice were given access to 2 bottles containing water and 1.5% NaCl and salt preference measured over 7 days. The role mineralocorticoid receptor (MR) in salt appetite was evaluated using spironolactone s.c.Basal water and sodium turnover and plasma sodium concentrations were not altered by the deletion of 11βHSD2 in the brain. When given access to NaCl brain specific 11βHSD2−/− mice displayed a significant salt preference, 70% of total fluid intake was accounted for by NaCl. Salt appetite was significantly reduced by MR blockade. Sodium was not retained in the null mice; increased salt intake resulted in significant natriuresis and polyuria.Deletion of 11βHSD2 in the brain, which is specifically expressed in the nucleus of the solitary tract (NTS) in mice, resulted in an increased salt appetite. Activation of MR is implicated since spironolactone significantly reduced NaCl intake. These data are the first demonstration of salt appetite occurring in the absence of sodium depletion and with normal renal function. They suggest that activation of MR on 11βHSD2 positive neurons in the NTS increases salt appetite. Funded by the British Heart Foundation.

Role of mineralocorticoid action in the brain in salt‐sensitive hypertension

1. The mechanisms by which excessive salt causes hypertension involve more than retention of sodium and water by the kidneys and are far from clear. Mineralocorticoids act centrally to increase salt appetite, sympathetic drive and vasopressin release, resulting in hypertension that is prevented by the central infusion of mineralocorticoid receptor (MR) antagonists. The MR has similar affinity for aldosterone and the glucocorticoids corticosterone or cortisol. Specificity is conferred in transport epithelia by the colocalization of the MR with 11β-hydroxysteroid dehydrogenase Type 2. Coexpression also occurs in some neurons, notably those of the nucleus tractus solitarius that are activated by sodium depletion and aldosterone and mediate salt-seeking behaviour. 2. The salt-induced hypertension of the Dahl salt-sensitive rat is mitigated by the central infusion of a mineralocorticoid antagonist even though circulating aldosterone is normal or reduced in salt-sensitive (SS). Contrary to reports that salt appetite in the Dahl salt-sensitive rat is depressed, we found that it is increased compared with that in Spraque-Dawley rats. 3. Extra-adrenal aldosterone synthesis in the brain occurs in minute amounts that could only be relevant locally. Expression of aldosterone synthase mRNA and aldosterone concentrations in the brain of Dahl salt-sensitive rats are increased compared with Spraque-Dawley rats. The central infusion of inhibitors of aldosterone synthesis lowers salt-induced hypertension in the Dahl salt-sensitive rat, suggesting a role for excessive Dahl salt-sensitive synthesis in the brain. Brain MR, particularly those in the paraventricular nuclei, regulate inflammatory processes that are exacerbated by sodium and lead to cardiovascular dysfunction.

The excess salt appetite of humans is not due to sodium loss in adulthood

In seeking the determinants of high salt intake, studies in rat have shown that sodium depletion in utero, neonatally, or in maturity, permanently enhances salt appetite. In humans too, salt appetite is permanently enhanced after perinatal sodium loss, but it is not known if sodium loss in adults also enhances salt intake. If it does, it might contribute to high sodium intake and its associated pathologies. Therefore, using methods that revealed the perinatal determinants of sodium appetite, here we evaluated whether salt appetite is enhanced in adults with a varied history of sodium loss. We find that putative sodium loss due to hyperhidrosis, hemorrhage, dehydration, or breastfeeding, does not increase salt appetite significantly. The findings contrast with the many studies showing enduring enhancement of salt appetite by perinatal sodium loss in humans, and suggest that lifelong salt appetite is established very early in development. In turn this counsels very early intervention to prevent lifelong excess sodium intake.

Gitelman Syndrome

Gitelman Syndrome

Glucocorticoids increase salt appetite by promoting water and sodium excretion

Glucocorticoids [e.g., corticosterone and dexamethasone (Dex)], when administered systemically, greatly increase water drinking elicited by angiotensin and sodium ingestion in response to mineralocorticoids [e.g., aldosterone and deoxycorticosterone acetate (DOCA)], possibly by acting in the brain. In addition, glucocorticoids exert powerful renal actions that could influence water and sodium ingestion by promoting their excretion. To test this, we determined water and sodium intakes, excretions, and balances during injections of Dex and DOCA and their coadministration (DOCA+Dex) at doses commonly employed to stimulate ingestion of water and sodium. In animals having only water to drink, Dex treatment greatly increased water and sodium excretion without affecting water intake, thereby producing negative water and sodium balances. Similar results were observed when Dex was administered together with DOCA. In animals having water and saline solution (0.3 M NaCl) to drink, Dex treatment increased water and sodium excretion, had minimal effects on water and sodium intakes, and was associated with negative water and sodium balances. DOCA treatment progressively increased sodium ingestion, and both water and sodium intakes exceeded their urinary excretion, resulting in positive water and sodium balances. The combination of DOCA+Dex stimulated rapid, large increases in sodium ingestion and positive sodium balances. However, water excretion outpaced total fluid intake, resulting in large, negative water balances. Plasma volume increased during DOCA treatment and did not change during treatment with Dex or DOCA+Dex. We conclude that increased urinary excretion, especially of water, during glucocorticoid treatment may explain the increased ingestion of water and sodium that occurs during coadministration with mineralocorticoids.

Glucocorticoids increase salt appetite by increasing urinary excretion

Glucocorticoids increase salt appetite by increasing urinary excretion

SGK1-dependent cardiac CTGF formation and fibrosis following DOCA treatment

The mineralocorticoids aldosterone and deoxycorticosterone acetate (DOCA) stimulate renal tubular salt reabsorption, increase salt appetite, induce extracellular volume expansion, and elevate blood pressure. Cardiac effects of mineralocorticoids include stimulation of matrix protein deposition leading to cardiac fibrosis, which is at least partially due to the direct action of the hormones on cardiac cells. The signaling mechanisms mediating mineralocorticoid-induced cardiac fibrosis have so far remained elusive. Mineralocorticoids have been shown to upregulate the serum- and glucocorticoid-inducible kinase 1 (SGK1), which participates in the effects of mineralocorticoids on renal tubular Na+ reabsorption and salt appetite. To explore the involvement of SGK1 in the pathogenesis of mineralocorticoid-induced cardiac fibrosis, SGK1 knockout mice (sgk1-/-) and wild-type littermates (sgk1+/+) were implanted a 21-day-release 50-mg DOCA pellet and supplied with 1% NaCl in drinking water for 18 days. This DOCA/high-salt treatment increased blood pressure in both genotypes but led to significant cardiac fibrosis only in sgk1+/+ but not in sgk1-/- mice. According to real-time polymerase chain reaction and Western blotting, DOCA/high-salt treatment enhanced transcript levels and protein expression of cardiac connective tissue growth factor (CTGF) only in sgk1+/+ but not in sgk1-/- mice. Furthermore, DOCA (10 microM) upregulated CTGF expression and enhanced CTGF promoter activity in lung fibroblasts isolated from sgk1+/+ but not from sgk1-/- mice, an effect involving spironolactone-sensitive mineralocorticoid receptors and activation of nuclear factor-kappaB (NFkappaB). Our results suggest that SGK1 plays a decisive role in mineralocorticoid-induced CTGF expression and cardiac fibrosis.

Increased salt appetite in patients with congenital adrenal hyperplasia 21-hydroxylase deficiency

Salt appetite was investigated in 14 patients with congenital adrenal hyperplasia of the salt-wasting form (SW group), 12 patients with the simple virilized form who are not salt losing, and 18 healthy siblings. Salt appetite was evaluated by questionnaire, preference tests, and dietary analyses. The findings showed that SW who were not therapeutically normalized showed increased salt appetite but no change in sweet preference. Their salt appetite correlated with symptoms of salt wasting, namely, plasma renin activity, plasma K(+), and urine Na(+) and (inversely) with blood pressure. Sensitivity to the taste of NaCl was not altered. Factor analyses of a larger group confirmed the distinction between salt appetite and sweet preference, but intake of dietary Na(+) and sweet carbohydrates and intake of salty and sweet snacks did not reflect distinct salt or sweet preferences. We confirm that putative perinatal dehydration, due to maternal nausea and vomiting during pregnancy, childhood vomiting, and diarrhea with occasional saline infusion, was related to increased salt appetite in adolescence. The findings suggest that salt appetite in humans is determined by interdependent, innate, physiological, and acquired attributes. Salt appetite in SW patients is an adaptive response mediated by the renin-angiotensin system, an innate predisposition to acquire salt preference (in anticipation of both sodium loss and its consequence), and imprinting by perinatal hyponatremic occurrences. Our findings contribute to understanding human salt intake, provide insight into the motivation for salt in patients with congenital adrenal hyperplasia 21-OH deficiency, and may point the way to improvements in therapeutic compliance in these patients.

Decreases in neurokinin-3 tachykinin receptor-immunoreactive and -mRNA levels are associated with salt appetite in the deoxycorticosterone-treated rat

Tachykinins are a family of neuropeptides that inhibit salt appetite. Although decreased tachykinin-mRNA levels are observed in natriorexic sodium-deplete rats, no decrease is seen in natriorexic sodium-replete rats that are administered the aldosterone-mimetic deoxycorticosterone acetate (DOCA). Since reduced synthesis of tachykinins could not account for increased appetite, we hypothesized that increased salt appetite was due to a downregulation of tachykinin receptors. Thus, we injected rats with DOCA once daily for 11 days and analyzed tachykinin receptor subtype, neurokinin 3 (NK3r)-immunoreactivity by Western blot analysis since intracerebroventricular injection of senktide (NK3r agonist) attenuates salt intake in DOCA-treated animals. We examined NK3r-immunoreactivity in several brain regions thought to be associated with the control of water and electrolyte balance including the bed nucleus of the stria terminalis, central nucleus of the amygdala, diagonal band of Broca, hippocampus, nucleus tractus solitarius, parabrachial nucleus, paraventricular nucleus of the hypothalamus, and supraoptic nucleus. Consistent with our hypothesis, we found decreased NK3r-immunoreactivity in all brain regions analyzed except for increases in the amygdala and no changes in the paraventricular nucleus of the hypothalamus. To examine whether DOCA’s effects on NK3r synthesis are direct, we used differentiated N1E-115 neuroblastoma cells that express NK3r and treated them with a range of concentrations of DOCA and found a dose-dependent decrease in NK3r-mRNA abundance via Northern blotting. The present results suggest that the tachykinin receptors are downregulated after subchronic DOCA treatment and this finding is consistent with the hypothesis that suppressed inhibition of salt appetite as mediated through the tachykininergic system.

Neuron-specific expression of human angiotensinogen in brain causes increased salt appetite.

The brain renin-angiotensin system (RAS) has an important role in the regulation of cardiovascular function. In the brain, angiotensinogen (AGT) is expressed mainly in astrocytes (glia) and in some neurons in regions controlling cardiovascular activities. Because of the inability to dissect the functional role of astrocyte- vs. neuron-derived AGT in vivo by pharmacological approaches, the exact role of neuron-derived AGT in the regulation of blood pressure (BP) and fluid and electrolyte balance remains unclear. Therefore, we generated a transgenic mouse model overexpressing human AGT under the control of a neuron-specific (synapsin I) promoter (SYN-hAGT). These mice exhibited high-level expression of human AGT mRNA in the brain, with lower expression in the kidney and heart. Human AGT was not detected in plasma, but in the brain it was expressed exclusively in neurons. Intracerebroventricular (30 ng) but not intravenous (500 ng) injection of purified human renin (hREN) caused a pressor response, which was prevented by intracerebroventricular preinjection of the angiotensin II type 1 receptor antagonist losartan, indicating an AT(1) receptor-dependent functional role of neuron-derived AGT in the regulation of BP in response to exogenous REN. Double transgenic mice expressing both the hREN gene and SYN-hAGT transgene exhibited normal BP and water intake but had an increased preference for salt. These data suggest that neuronal AGT may play an important role in regulating salt intake and salt appetite.

Glucocorticoid and mineralocorticoid regulation of angiotensin II type 1 receptor binding and inositol triphosphate formation in WB cells.

Mineralocorticoids, glucocorticoids, and angiotensin II (AngII) act cooperatively to maintain body fluid homeostasis. Mineralocorticoids, such as aldosterone and deoxycorticosterone-acetate (DOCA), function synergistically with AngII in the brain to increase salt appetite and blood pressure. In addition, glucocorticoids increase AngII-induced drinking and pressor responses and may also facilitate the actions of aldosterone on salt appetite. The AngII Type 1 (AT1) receptor mediates many of the physiological and behavioral actions of AngII. This receptor is coupled to the G-protein Gq, which mediates AngII-induced inositol triphosphate (IP3) formation. The WB cell line, a liver epithelial cell line that expresses the AT1 receptor, was used to examine the cellular basis of glucocorticoid and mineralocorticoid regulation of AT1 function. In this study corticosterone and dexamethasone treatments increased the number of AT1 receptors by activating the glucocorticoid receptor (GR). This increase in AT1 binding resulted in enhanced AngII-stimulated IP3 formation. However, only supraphysiological doses of aldosterone or DOCA increased AT1 binding, and this effect also was mediated by GR activation. Furthermore, despite evidence that mineralocorticoids and glucocorticoids function together to increase AngII-stimulated actions in vivo, aldosterone and dexamethasone did not act synergistically to affect AT1 binding, Gq expression, or IP3 formation. These results indicate that GR activation, and the subsequent increases in AT1 binding and in AngII-stimulated IP3 formation, may represent a cellular mechanism underlying the synergy between adrenal steroids and AngII.

Increased sodium appetite stimulates c- fos expression in the organum vasculosum of the lamina terminalis

The relation between c- fos expression in the forebrain of Lister hooded rats and water and NaCl intakes was examined in response to systemic injection of angiotensin II, desoxycorticosterone, angiotensin II and desoxycorticosterone together, frusemide or low sodium diet, all treatments that induce a sodium appetite. Angiotensin II (1 mg/kg subcutaneously) caused significant increases in the 1-h intakes of water and 1.8% NaCl compared to controls, the effect on water intake being the greater. There was a similar increase in NaCl intake after four days' treatment with desoxycorticosterone (20 mg pellet subcutaneously) but water intake was not increased. The NaCl intake of rats given angiotensin II following desoxycorticosterone treatment was approximately the sum of the intakes after angiotensin II or desoxycorticosterone alone, but the water intake was slightly less than after angiotensin II alone. Frusemide pretreatment (4 mg/kg subcutaneously) caused an NaCl intake similar to that following angiotensin II and desoxycorticosterone but water intake was little affected. Low dietary sodium also increased salt appetite, as expected. These treatments were repeated in rats that were not allowed to drink NaCl, after which the brains were processed for c- fos immunocytochemistry. This showed intense staining of the subfornical organ, median preoptic nucleus, organum vasculosum of the laminal terminalis, paraventricular nucleus and supraoptic nucleus after subcutanous angiotensin II. Animals given angiotensin II following desoxycorticosterone pretreatment showed patterns of c- fos expression that did not differ from those of angiotensin II alone. Treatment with desoxycorticosterone alone produced intense staining in the organum vasculosum of the laminal terminalis and some staining in the median preoptic nucleus. Frusemide gave a similar pattern of staining to desoxycorticosterone, stimulating c- fos expression in the same regions but to a lesser extent. A low salt diet resulted in increased c- fos expression only in the organum vasculosum of the laminal terminalis. Therefore, five different treatments that induced increased sodium appetite evoked distinct patterns of c- fos expression in the anteroventral region of the third ventricle of the rat forebrain. Since the common feature was induction of c- fos in the organum vasculosum of the laminal terminalis, these results suggest a key role for this structure in the development of increased sodium appetite.

Sympathetic nervous system influences salt appetite in four strains of rats

Sodium appetite and preference were examined in four rat strains using a social stressor and drugs to block sympathetic nervous system (SNS) activity. We have studied these strains for over 14 yr in our laboratory and the SHR strain has increased blood pressure and increased sympathetic nerve activity. The F 1 crosses produce male offspring with the Y chromosome from a hypertensive or normotensive father, to examine its influence on sodium appetite. The pharmacological manipulation produces blockages of the SNS which may be partially responsible for stress induced sodium appetite. The objectives were to determine: (i) if the SNS was necessary for stress induced increased salt appetite; and (ii) if the Y chromosome from a hypertensive father increased salt intake or preference. Four strains ( n = 6–8/group) of male rats were studied from 3–6 mo of age: normotensive Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and hybrid crosses between a WKY mother and SHR father (WS) and the reciprocal cross (SW). Each group consumed Purina rat chow (0.3% Na) and was given a four-bottle choice of salt water ad lib (0.0%, 0.5%, 1.0%, and 1.5% NaCl). Social stress produced by intruder males significantly increased salt intake in all groups. SHR had higher salt intake than WKY both before and after exposure to intruder stress. In general, the SHR group preferred twice the concentration of saline (1.0%) as did the WKY (0.5%). Clonidine and reserpine both reduce SNS activity and consequently reduced salt intake stress, from 20–44% depending on the genetic background of the rat strain. The SNS was necessary for stress induced increased salt appetite and the Y chromosome from a hypertensive father did not elevate salt appetite.

Salt consumption and body fluid balance during cold exposure in rats

We investigated the effect of exposure to cold on salt consumption and the role of salt consumption on the maintenance of body fluid balance in male Wistar rats. The rats were provided with both tap water and NaCl solution ad lib during 16-h exposure to cold (10°C) and normal (25°C) air temperature conditions. The concentration of the NaCl solution was 0.9% for one group (0.9% NaCl group; n = 7) and 1.8% for the other (1.8% NaCl group; n = 6). At 10°C, weight loss was greater than that at 25°C, and fluid and Na balance were negative in the 0.9% NaCl group. However, the calculated Na concentration of the fluid consumed in the 0.9% NaCl group was about 135 mEq/l Na (0.8% NaCl) at both 10°C and 25°C. In the 1.8% NaCl group, the values indicating fluid and Na balance under both temperature conditions were similar, while the calculated concentration of Na in fluid consumed at 10°C (187 mEq/l Na: 1.1% NaCl) was higher than that at 25°C (153 mEq/l Na: 0.9% NaCl). These results suggest that the consumption of hypertonic NaCl solution indicating increased salt appetite during exposure to cold counteracts the loss of body fluid and Na via urine.

Extracellular dehydration during pregnancy increases salt appetite of offspring

The propensity to prefer and to consume salty foods varies considerably from person to person, and excessive salt intake has been linked to a number of pathological conditions. Extracellular dehydration occurs in humans after vomiting or diarrhea and is commonly observed during pregnancy. Because the hormonal responses to extracellular dehydration are known to increase salt appetite, we tested the hypothesis that extracellular dehydration during pregnancy increases the propensity of offspring to consume salt. Pregnant rats were treated with polyethylene glycol, which is known to produce extracellular dehydration and to exaggerate sodium appetite. The offspring of these treated pregnant rats showed an increase in salt appetite as compared with the offspring of control untreated dams. These results demonstrate that extracellular dehydration during pregnancy can enhance the natriophilic propensity in offspring and suggest that gravidic vomiting may contribute to the epidemiological factors of hypertension and other pathologies.

Salt Appetite, Body Sodium, Handling of a NaCl Load, Renin, and Aldosterone in Genetically and Spontaneously Hypertensive Rats

Salt appetite, body sodium, handling of a NaCl load, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were compared in New Zealand genetically hypertensive (GH) and Japanese spontaneously hypertensive rats (SHRs) and their respective normotensive controls [normal Wistar (N) and Wistar-Kyoto (WKY) rats]. Salt appetite was increased in SHRs compared with GH, N, and WKY rats when rats were on salt-free chow and given a choice of distilled water and NaCl solution. Body sodium, measured by whole body counting, was higher in SHRs than in the other strains but did not differ among GH, N, and WKY rats. The rate of excretion of a NaCl load was not increased in GH rats and was slightly increased in SHRs only when on a very low NaCl intake. PRA and PAC (radioimmunoassay) were lower in SHRs than in GH, N, and WKY rats. PAC had a significant negative correlation with body sodium across the four strains. There is no evidence of any abnormality in sodium regulation in GH rats. However, the SHRs have an increased salt appetite and an increased body sodium even when sodium intake is limited; PRA and PAC appear to have responded appropriately to the increased body sodium.