Intake Of Salt Solutions Research Articles

Mineralocorticoid modulation of central angiotensin-induced neuronal activity, water intake and sodium appetite

Central angiotensin II (AngII) stimulates water and salt solution intake. Pretreatment with low-dose mineralocorticoid (DOCA) enhances this AngII-induced intake of salt solutions (the synergy theory) in Wistar and Sprague Dawley rats but not in Fischer rats. This response is mediated via the AT-1 receptor. Electrophysiological experiments using iontophoretic application of AngII and the AT-1 receptor-specific non-peptide antagonist losartan showed excitation of neurons in the preoptic/medial septum region of urethane-anesthetized male Wistar rats. DOCA pretreatment further enhances this neuronal excitation in response to AngII and reduces the responses to losartan. This generated the hypothesis that DOCA-enhanced AngII-induced neuronal excitation is the neural support for the synergy theory. AT-2 receptors modulate these intake responses depending on sodium in the diet, and diuretic-induced dehydration during pregnancy produces a higher salt intake in the offspring. AngII-induced salt and water intakes were tested in offspring from Sprague Dawley mothers with only 1.8% NaCl to drink in which half were treated with furosemide. The important observations were a) the AT-1 antagonist alone suppressed intakes in offspring from mothers not treated with furosemide, b) both AT-1 and AT-2 antagonists suppressed intakes in offspring from furosemide-treated mothers, and c) combined administration of AT-1 and AT-2 antagonists greatly suppressed water intake in offspring from mothers not treated with furosemide. These results suggest that AT-1 and AT-2 receptors have variable properties (receptor number and/or second messengers). Furthermore, the activity and function of these central AngII receptors depend on the background mineralocorticoid levels. The exact mechanism of this influence, however, remains to be determined.

Mineralocorticoid modulation of central angiotensin-induced neuronal activity, water intake and sodium appetite

Central angiotensin II (AngII) stimulates water and salt solution intake. Pretreatment with low-dose mineralocorticoid (DOCA) enhances this AngII-induced intake of salt solutions (the synergy theory) in Wistar and Sprague Dawley rats but not in Fischer rats. This response is mediated via the AT-1 receptor. Electrophysiological experiments using iontophoretic application of AngII and the AT-1 receptor-specific non-peptide antagonist losartan showed excitation of neurons in the preoptic/medial septum region of urethane-anesthetized male Wistar rats. DOCA pretreatment further enhances this neuronal excitation in response to AngII and reduces the responses to losartan. This generated the hypothesis that DOCA-enhanced AngII-induced neuronal excitation is the neural support for the synergy theory. AT-2 receptors modulate these intake responses depending on sodium in the diet, and diuretic-induced dehydration during pregnancy produces a higher salt intake in the offspring. AngII-induced salt and water intakes were tested in offspring from Sprague Dawley mothers with only 1.8% NaCl to drink in which half were treated with furosemide. The important observations were a) the AT-1 antagonist alone suppressed intakes in offspring from mothers not treated with furosemide, b) both AT-1 and AT-2 antagonists suppressed intakes in offspring from furosemide-treated mothers, and c) combined administration of AT-1 and AT-2 antagonists greatly suppressed water intake in offspring from mothers not treated with furosemide. These results suggest that AT-1 and AT-2 receptors have variable properties (receptor number and/or second messengers). Furthermore, the activity and function of these central AngII receptors depend on the background mineralocorticoid levels. The exact mechanism of this influence, however, remains to be determined.

Long term dietary methoxychlor exposure in rats increases sodium solution consumption but has few effects on other sexually dimorphic behaviors

Methoxychlor is an insecticide with estrogen-like activity, thus exposure during development might cause sexually dimorphic behavioral alterations. To evaluate this, pregnant rats consumed diets containing 0, 10, 100 or 1000 ppm methoxychlor from gestational day 7, and offspring continued on these diets until postnatal day (PND) 77. Assessments of sexually dimorphic behaviors in offspring indicated that intake of a 3.0% sodium chloride solution was significantly increased (41%) in males and females of the 1000 ppm group. No treatment group differed from controls in open field nor running wheel activity, play behavior, nor 0.3% saccharin solution intake. Offspring of the 1000 ppm group showed significantly decreased body weight, reaching 17% less than controls at PND 77, but not clearly related to their salt solution intake. During pregnancy, 1000 ppm dams consumed 23% less food and weighed 10% less than controls, but this did not affect litter outcomes. These results indicate that in rodents, developmental and chronic exposure to dietary methoxychlor alters the sexually dimorphic behavior of salt-solution intake in young adults of both sexes. Similar behavioral alterations with other xenoestrogens, and the potential for interactions among xenoestrogens, suggest that this report may minimize the true effects of dietary methoxychlor exposure.

Central AII evokes a normal sodium appetite in the Fischer rat, but its low spontaneous sodium intake may be related to reduced excitation and increased inhibition in septo-preoptic AII neurons

Fischer rats show a low or absent basal salt appetite and a reduced intake of salt solutions in response to peripherally administered angiotensin II (AII) when compared to other strains. We investigated spontaneous sodium intake, and sodium intake after intracerebroventricular (i.c.v.) AII and losartan, and septo-preoptic neuronal responses to AII and losartan, in age-matched male Fischer and Wistar rats. Spontaneous intake of 1.8% NaCl was lower in Fischers, but i.c.v. injection of 10 pmol AII produced similar 2 h intakes in a 2 h test period. Iontophoretic application of AII and losartan onto neurons in the septo-preoptic continuum revealed differences between the two strains of rat. In the Fischer rats only 11% of the spontaneously active neurons were sensitive to locally applied AII compared to approximately 30% in the Wistar. Local application of losartan produced neuronal inhibition in Fischer rats but neuronal excitation in Wistars. The central AII system appears to be regulated differently in these two strains, and may be related to the differences in their spontaneous sodium intake, but not to AII aroused sodium appetite.

Involvement of Mesolimbic Structures in Short-Term Sodium Depletion: In situ Hybridization and Ligand-Binding Analyses

Acute treatment with the diuretic furosemide (Lasix) produces a reduction in plasma Na⁺ and volume as well as increased thirst and salt appetite. The resulting hypovolemia stimulates the well-known counter-regulatory physiological response from the renin-angiotensin-aldosterone system. However, the neurochemical players underpinning the behavioral responses of thirst and salt appetite are less clear. Previously, we have reported that salt-replete deoxycorticosterone (DOCA) treatment activates mesolimbic structures associated with reward and goal-seeking behavior. The present study was designed to test whether the same brain regions are affected in a salt-depleted state. In experiment 1, two groups of adult male Sprague-Dawley (SD) rats were injected with Lasix (10 mg/rat, s.c.) and 18 h later were allowed access either to 2% NaCl solution (‘Lasix+salt’) or only to tap water (‘Lasixnosalt’) for 2 h. For comparison purposes, a third group received an isotonic saline injection instead of Lasix and was allowed access to the 2% salt solution (Vehicle). All groups were permitted 24 h access to tap water. We found no differences in dynorphin-mRNA levels in any striatal and accumbal regions among any of the treatment groups. However, as found previously in DOCA-treated rats, there were increased enkephalin (ENK)-mRNA and decreased dopamine transporter (DAT) binding levels throughout the striatum in Lasix+salt and decreased ENK-mRNA in Lasixnosalt rats versus Vehicle. In experiment 2, the involvement of the ENKergic and/or dopaminergic system was tested in rats divided into the same three groups described in experiment 1. However, before access to salt or water, the Lasix+salt and the vehicle groups were administered either a δ-opioid, naltrindole or a dopamine D₂ antagonist, raclopride. Only the naltrindole-treated rats showed a blunted intake of salt solution. Thus, these findings along with our neurochemical results suggest that mesolimbic enkephalin might impact salt intake through dopaminergic systems.

Effect of sodium deprivation on morphine-and lithium-induced conditioned salt avoidance and taste reactivity.

When paired with morphine, rats suppress their intake of saccharin solution, but not a less palatable salt solution. The reward comparison hypothesis argues that when a taste is paired with morphine, intake of the solution is expected to decrease as the palatability of the taste increases. Therefore, morphine should more effectively suppress intake of salt solution in rats that are conditioned in a sodium-deprived state than in rats that are conditioned in a sodium-replete state. The present experiments evaluated the effect of furosemide-induced sodium deprivation on morphine and lithium-induced salt (experiment 1) and saccharin (experiment 2) avoidance and salt taste reactivity (experiment 4). Rats were injected with furosemide or saline 21 h prior to access to salt solution (experiments 1 and 3) or saccharin solution (experiment 2). Immediately following access to the solution, the rats were injected with saline, morphine or lithium chloride solution. In experiments 1 and 2, a two-bottle test measured the strength of the taste preference/avoidance. In experiments 3 and 4, the taste reactivity test evaluated the furosemide-induced unconditional palatability changes for salt solution (experiment 3) and the conditional palatability changes for salt previously paired with morphine or lithium (experiment 4). Sodium depletion induced by furosemide pretreatment conditionally enhanced subsequent preference for salt solution using both the taste avoidance test (experiment 1) and the taste reactivity test (experiment 4). Salt-lithium associations, but not salt-morphine associations, suppressed salt preference. However, the salt-morphine (40 mg/kg) association enhanced salt preference (in both experiments 1 and 4) when rats were conditioned in a sodium-deprived state. In experiment 2, morphine-saccharin associations resulted in conditioned saccharin avoidance regardless of pretreatment condition. When the palatability of salt was enhanced by sodium depletion, morphine produced a mild conditioned salt preference in both a two-bottle preference test and enhanced ingestion reactions in the taste reactivity test, but morphine produced conditioned saccharin avoidance.

Infant Salt Preference and Mother's Morning Sickness

Evidence for an association between early pregnancy sickness and offspring salt (NaCl) preference has been obtained from studying offspring as young adults. To determine whether effects on NaCl preference are expressed in infancy, the present study examined 16-week-old infants whose mothers reported either little or no vomiting (N= 15) or frequent moderate to severe vomiting (N= 14) during the first 14 weeks of their pregnancy. The infants' oral-motor facial reactions to each solution and their relative intakes of distilled water and 0·1mand 0·2mNaCl were used as measures of preference. Infants of mothers who reported no or mild symptoms had a significantly lower relative intake of salt solutions than infants whose mothers reported moderate to severe symptoms (p< 0·01). The former infants also showed a greater number of aversive facial responses when given 0·2mNaCl (p< 0·05). Taken together, these findings support the hypothesis that maternal dehydration, induced by moderate to severe vomiting during pregnancy, can lead to enhanced salt preference in offspring. They also provide a potential explanation for some of the variability encountered when human infants are tested for their salt preference.

Effects of preferential delta and kappa opioid receptor agonists on the intake of hypotonic saline

A previous study has implicated central mu opioid receptors in the preference for salt solutions. Because mu, kappa and delta receptors are all thought to play a role in food intake and/or the mediation of palatability, we performed a series of experiments to determine whether preferential agonists at kappa and delta receptors might also stimulate the intake of salt solutions. When injected centrally into nondeprived rats, two selective agonists at delta receptors caused increases in the intake of 0.6% saline; the intake of concurrently available water was either unchanged or slightly increased. The selective kappa agonist U-50, 488H had no effect on water or saline intake, whereas the preferential kappa agonist DAFPHEDYN caused a delayed increase in saline intake. These results indicate a role for central delta receptors in the preference for salt solutions, and are consistent with the suggestion that opioids play a role in the mediation of palatability.

Durability of Rock as Function of Grain Size, Pore Size, and Rate of Capillary Absorption of Water

A series of experiments were performed to determine the relationship of grain and pore size to the capillary absorption of rock and the level to which water will naturally penetrate when the rock is exposed to it. As expected, the fine grained rocks showed the fastest rate and highest penetration of water and salt solution. Rates were found to be log-normally distributed—fast initial absorption, slower subsequent absorption. A correlation was found between rates of absorption and durability. High rate of absorption specimens were less durable during freezing and thawing than rocks with a low rate of absorption. All other conditions, such as mineralogy and environment, being constant, it is concluded that finer grained rocks, because of their more rapid water and salt solution intake, tend to deteriorate and weather faster than coarser grained equivalents. The results indicate the importance of grain size and pore size in assessment of the long term durability of rock when used as construction material.

SELF-SELECTION OF SALT BY GILTS DURING PREGNANCY AND LACTATION

There were two feeding experiments, in which feed was available free choice with 18 gilts in the first and 14 gilts in the second, and a metabolism trial, in which feed was restricted, with two pairs of gilts. Equal numbers of pregnant (P) and non-pregnant (NP) gilts were used; the terms "farrow" and "lactation" were applied to the NP gilts on a time basis only. In the first experiment and the 16-wk metabolism trial, a salt-deficient diet was fed, but in the second experiment the diet contained 0.5% added salt; all gilts had access to both water and a 0.5% salt solution. Considerable variation among gilts in both water and salt solution intake was evident, and there seemed to be a response to a taste preference rather than to a dietary need. During lactation, the intakes of salt solution and of total salt by the P gilts were approximately twice that of the NP gilts. Although consuming 78% more sodium from the salt solution, the P gilts did not lose in the feces and urine much more sodium than did the NP gilts; therefore, with equal feed intake, sodium retention appeared greater in the P gilts.

Increased sodium intake is somehow induced in rats by intravenous angiotensin II

Adult male rats maintained on dry food, water, and 3% NaCl solution received continuous infusion of angiotensin II (A II) via right atrial catheters. A II was delivered in 0.315 ml/hr at doses of 15, 30, and 60 ng/min/rat for 3 to 5 days. At the higher doses mean daily salt solution intake rose from very low preinfusion levels to 18.7 and 19.6 ml, respectively. Daily water intakes increased in some animals and decreased in others on the first day of infusion but were double preinfusion levels by the second day. Persistence of the sodium appetite after the end of A II infusion was seen in most of the rats which received the highest dose. The mechanisms which might underlie the effect of blood-borne A II on sodium intake are discussed and three possibilities considered: (1) that A II may act on the brain to stimulate sodium appetite, (2) that A II may act via the adrenal cortex, and that the sodium appetite may arise as a result of increased plasma levels of adrenal steroids, and (3) that A II may act via the kidney, producing a natriuresis. According to this view, sodium appetite would arise as a result of loss of body sodium and/or blood volume.

Salt seeking by means of food and fluid selection in adrenalectomized rats

An experiment involving several changes in the salt content of food and solutions investigated the generality of salt-seeking behavior in adrenalectomized rats. Salt-solution intake varied as a function of NaCl concentration. The intake of sodium is relatively unaffected by the concentration of NaCl in the food as long as NaCl in solution is available. But when the salt solution is removed, salt seeking and sodium regulation takes place by way of salt in the food.

The effects of surgical desalivation of the rat upon taste acuity

Taste acuity in control and surgically desalivated rats was evaluated with a two-bottle preference test. Rats were presented with a choice between water and various concentrations of Nacl, HCl and quinine sulphate (QS) solutions. Intake of the latter solutions was expressed as a percentage of the total intake. Total volume intake was expressed as ml intake/g body weight. When presented with a choice between the water and salt solutions, both immediately and 7 months after desalivation, experimental rats showed a variable response as compared to controls, suggesting some type of abnormality in regulation of salt solution intake. Control rats showed a marked rejection of the HCl (range 5.2–16 per cent) and QS (range 4.2–11.8 per cent) solutions while the desalivated rats showed significantly less rejection (range 25–57.4 per cent for HCl and 73.7–31.8 per cent for QS). On most test days, volume intake of the desalivates was greater than the controls, both immediately and 7 months after desalivation. The data suggest a decrease in taste acuity in rats without normal salivary flow.

Effect of desoxycorticosterone acetate on NaCl appetite of propylthiouracil-treated rats

Dietary administration of the antithyroid drug, propylthiouracil (1.0 g/kg food), to rats induced a spontaneous salt appetite when choice was offered between 0.15 M NaCl solution and water to drink. The per cent change in intake of 0.15 M NaCl solution was reduced from control by administration of desoxycorticosterone acetate (DOCA) up to a level of 200 μg/day (approximately 100 μg/100 g b wt/day). Doses of DOCA greater than this returned percent change in intake of NaCl solution toward the level of untreated controls. Thus, a U-shaped dose-response relationship existed between per cent change in NaCl intake from control and logarithm of dose of DOCA administered. The per cent change in water intake tended to be a mirror image of NaCl intake. The effect on intake of salt solution may be specific for compounds with mineralocorticoid activity since graded dose levels of either corticosterone acetate (a glucocorticoid) or estrone failed to affect intakes significantly. Administration of purified renal extract at graded dose levels also failed to influence intakes significantly. The results suggest, but do not prove, that blood level of mineralocorticoid influences spontaneous intake of NaCl solution in the rat.

SALT HUNGER UNAFFECTED BY CADMIUM IN RATS ALLOWED SALINE SOLUTION BY CHOICE.

Forty weanling rats were given choices of sodium chloride solution or water to drink until 8.4 months of age and again from 23 months of age until death, half of the rats receiving small doses of cadmium. No differences in intakes appeared in control and cadmium-fed groups. Young females drank two and one-half times as much salt solution as did males and older ones five times as much. When not exposed to salt, fluid intake of females remained elevated; that of males did not. Upon re-exposure, intake of salt solution by females almost doubled from previous levels, but changed little in males. Excessive intakes of more than 180 mg NaCl/100 g body wt. daily appeared in 6 of 20 older females, whereas 10 of 14 males exhibited aversion to salt. Young female rats allowed salt solution or water rapidly acquire salt hunger which may become excessive later in life.