Osmoregulation in water-deprived rats drinking hypertonic saline: effect of area postrema lesions

Rats drank rapidly when 0.3 M NaCl was the only drinking fluid available after overnight water deprivation, consuming approximately 200 ml/24 h. Although such large intakes of this hypertonic solution initially elevated plasma osmolality, excretion of comparable volumes of urine more concentrated than 300 meq Na(+)/l ultimately appears to restore plasma osmolality to normal levels. Rats drank approximately 100 ml of 0.5 M NaCl after overnight water deprivation, but urine Na(+) concentration (U(Na)) did not increase sufficiently to achieve osmoregulation. When an injected salt load exacerbated the initial dehydration caused by water deprivation, rats increased U(Na) to void the injected load and did not significantly alter 24-h intake of 0.3 or 0.5 M NaCl. Rats with lesions of area postrema had much higher saline intakes and lower U(Na) than did intact control rats; nonetheless, they appeared to osmoregulate well while drinking 0.3 M NaCl but not while drinking 0.5 M NaCl. Detailed analyses of drinking behavior by intact rats suggest that individual bouts were terminated by some rapid postabsorptive consequence of the ingested NaCl load that inhibited further NaCl intake, not by a fixed intake volume or number of licks that temporarily satiated thirst.     

Circulating angiotensin II mediates sodium appetite in adrenalectomized rats

We investigated the role of circulating ANG II in sodium appetite after adrenalectomy. Adrenalectomized rats deprived of their main access to sodium (0.3 M NaCl) for 9 h drank 14.1 +/- 1.5 ml of the concentrated saline solution in 2 h of access. Intravenous infusion of captopril (2.5 mg/h) during the last 5 h of sodium restriction reduced sodium intake by 77 +/- 12% (n = 5) without affecting the degree of sodium depletion and hypovolemia incurred during deprivation. Functional evidence indicates that this dose of captopril blocked production of ANG II in the peripheral circulation, but not in the brain; that is, injection of ANG I into the lateral brain ventricle stimulated intake of both water and 0.3 M NaCl. Intravenous infusion of ANG II (starting 10-15 min before 0.3 M NaCl became available) in adrenalectomized, captopril-treated rats restored both sodium intake and blood pressure to values seen in rats not treated with captopril. Longer (20 h) infusions of captopril in 22-h sodium-restricted rats also blocked sodium appetite, but reduced or prevented sodium depletion. Intravenous infusion of ANG II after these long captopril infusions stimulated sodium intake, but intake was less than in controls not treated with captopril. These results indicate that most or all of the sodium appetite of adrenalectomized rats is mediated by circulating ANG II.     

Effects of hypotension and fluid depletion on central angiotensin-induced thirst and salt appetite

We examined the effects of hypotension and fluid depletion on water and sodium ingestion in rats in response to intracerebroventricular infusions of ANG II. Hypotension was produced by intravenous infusion of the vasodilator drug minoxidil (25 microg x kg(-1) x min(-1)) concurrently with the angiotensin-converting enzyme inhibitor captopril (0.33 mg/min) to prevent endogenous ANG II formation. Hypotension increased water intake in response to intracerebroventricular ANG II (30 ng/h) but not intake of 0.3 M NaCl solution and caused significant urinary retention of water and sodium. Acute fluid depletion was produced by subcutaneous injections of furosemide (10 mg/kg body wt) either alone or with captopril (100 mg/kg body wt sc) before intracerebroventricular ANG II (15 or 30 ng/h) administration. Fluid depletion increased water intake in response to the highest dose of intracerebroventricular ANG II but did not affect saline intake. In the presence of captopril, fluid depletion increased intakes of both water and saline in response to both doses of intracerebroventricular ANG II. Because captopril administration causes hypotension in fluid-depleted animals, the results of the two experiments suggest that hypotension in fluid-replete animals preferentially increases water intake in response to intracerebroventricular ANG II and in fluid-depleted animals increases both salt and water intake in response to intracerebroventricular ANG II.     

NaCl concentration alters temporal patterns of drinking and eating by rats

To obtain an understanding of the role of taste in NaCl preference-aversionunder standard laboratory feeding conditions, we characterizedthe eating and drinking patterns of rats maintained on powderedfood, water, and NaCl solution. The concentration of NaCl wasvaried systematically from 0.01 to 0.4 M with a single concentrationpresent for four consecutive days. In addition to daily intake,the number and duration of ingestion bouts, and the number ofswitches between food and fluid and between water and salinewere recorded throughout the day/night cycle. The availabilityof NaCl solution did not alter the typical pattern of night-timefeeding and prandial (drinking after a meal) drinking. As shownpreviously, NaCl intake was highest for 0.15 M NaCl and declinedat both stronger and weaker concentrations. Variations in drinkingbout number and duration determined amount consumed. Drinkingbout duration was highest for 0.2 M NaCl then declining progressivelyat both stronger and weaker concentrations. The number of drinkingbouts was highest for 0.04 M NaCl, a concentration slightlyabove the adapting salivary sodium concentration, declininglinearly thereafter with stronger NaCl concentrations. The availabilityof NaCl solution influenced the amount of food consumed, aswell as the number and duration of food bouts. Food bout numberwas highest in the presence of the weakest 0.01 M NaCl solution,while food bout duration was highest in the presence of hypertonicNaCl concentrations. Most switching behavior occurred betweenmeal consumption and drinking and little between drinking fluids.When 0.01–0.08 NaCl solutions were available, the ratsdrank saline after a meal; when hypertonic 0.3–0.4 M NaClsolutions were available, they drank water after a meal. Inthe presence of intermediate NaCl concentrations (0.15–0.20),the choice of fluid consumed after a meal was more equivocalto the extent that there was increased switching between waterand saline and vice versa. The significance of these differencesin the micromolar features of eating and drinking are discussedin relationship to taste and postingestional control mechanismsof ingestion.     

Centrally administered vasopressin cross-sensitizes rats to amphetamine and drinking hypertonic NaCl

Prior sodium restriction cross-sensitizes rats to the psychomotor effects of amphetamines and vice versa. Repeated central injections of vasopressin (VP) induce a psychomotor sensitization similar to amphetamine sensitization and repeated sodium deficiency. Thus brain VP signaling may be a common mechanism involved in mediating these two motivational systems. In experiment 1, we tested the hypothesis that rats previously sensitized to central VP would show enhanced psychomotor responses to amphetamine. Rats were administered saline, VP (50 ng), or amphetamine (1 mg/kg or 3 mg/kg) on days 1 and 2, and given saline or amphetamine on day 3. Amphetamine produced psychomotor arousal in all groups. However, amphetamine on day 3 elicited a significantly greater psychomotor response in rats that had prior injections of amphetamine or VP than in rats previously treated with saline. In experiment 2, the hypothesis that prior experience with central VP would cross-sensitize rats to drinking hypertonic sodium (NaCl) solutions was tested. Rats were administered VP (50 ng) or saline for 3 days. On the fourth day, nondeprived rats were given access to 0.3 M NaCl and water for 1 h. Control and saline-treated rats only drank 1 ml of 0.3 M NaCl, but rats previously exposed to central VP drank significantly more hypertonic saline (4 ml). These results show that prior experience with central VP cross-sensitizes rats to the psychomotor stimulant effects of amphetamine and the ingestion of concentrated NaCl solutions. This pattern of cross-sensitization links central VP signaling, amphetamine, and sodium deficiency, and therefore it may play a role in the cross-sensitization between sodium appetite and amphetamines.     

Presystemic influences on thirst, salt appetite, and vasopressin secretion in the hypovolemic rat

The present studies investigated the influence of presystemic signals on the control of thirst, salt appetite, and vasopressin (VP) secretion in rats during nonhypotensive hypovolemia. Rats were injected with 30% polyethylene glycol (PEG) solution, deprived of food and water overnight, and then allowed to drink water, 0.15 M NaCl, or 0.30 M NaCl. The PEG treatment, which produced 30-40% plasma volume deficits, elicited rapid intakes in an initial bout of drinking, but rats consumed much more 0.15 M NaCl than water or 0.30 M NaCl. In considering why drinking stopped sooner when water or concentrated saline was ingested, it seemed relevant that little or no change in systemic plasma Na(+) concentration was observed during the initial bouts and that the partial repair of hypovolemia was comparable, regardless of which fluid was consumed. In rats that drank 0.15 M NaCl, gastric emptying was fastest and the combined volume of ingested fluid in the stomach and small intestine was largest. These and other observations are consistent with the hypothesis that fluid ingestion by hypovolemic rats is inhibited by distension of the stomach and proximal small intestine and that movement of dilute or concentrated fluid into the small intestine provides another presystemic signal that inhibits thirst or salt appetite, respectively. On the other hand, an early effect of water or saline consumption on VP secretion in PEG-treated rats was not observed, in contrast to recent findings in dehydrated rats. Thus the controls of fluid ingestion and VP secretion are similar but not identical during hypovolemia.     

NaCl intake and preference threshold of spontaneously hypertensive rats.

Both male and female spontaneously hypertensive (SH) rats have an appetite for NaCl solution. The appetite is present when a choice is offered between distilled water and either isotonic or hypertonic (0.25 M) NaCl solution to drink. Total fluid intake (water plus NaCl solution) was greater for SH rats than for controls while food intakes (g/100 g body wt/day) of SH rats were not different from controls. Mean body weight of SH rats was always less than that of controls. The appetite for NaCl solution was accompanied by a significant reduction in preference (detection) threshold. SH rats could detect the difference between distilled water and NaCl solution when the concentration of the latter was 12 mEq/liter compared to a control threshold of 30 mEq/liter. The NaCl appetite and reduced NaCl preference threshold induced by spontaneous hypertension is in marked contrast to the NaCl aversion induced by other types of experimentally induced hypertension in rats. The mechanism or mechanisms responsible for these differences remain for further study.     

Water ingestion provides an early signal inhibiting osmotically stimulated vasopressin secretion in rats

Dehydrated dogs are known to inhibit secretion of vasopressin (VP) within minutes after drinking water, before plasma osmolality (P(osmol)) diminishes. The present studies determined whether water ingestion causes a similar rapid inhibition of neurohypophyseal hormone secretion in rats. Adult rats were infused with 1 M NaCl (2 ml/h iv) for 240 min to stimulate VP and oxytocin (OT) secretion. After 220 min of infusion, rats were given water to drink for 5 min, and blood samples were taken 5 and 15 min later for RIA. Plasma VP (pVP) was much lower when rats ingested water than when they drank nothing even though P(osmol) was not significantly altered. Plasma OT (pOT) was affected similarly. In contrast, no effects on pVP or pOT occurred when rats drank isotonic NaCl solution for 5 min in amounts comparable to the water intakes (approximately 5.5 ml). These results suggest that neurohypophyseal secretion of VP and OT in rats is inhibited rapidly by water drinking, and that this inhibition is mediated by a visceral signal of osmotic dilution rather than by the act of drinking per se.     

Water ingestion by rats fed a high-salt diet may be mediated, in part, by visceral osmoreceptors

After surgical removal of all salivary secretions ("desalivation"), rats increase their consumption of water while eating dry laboratory chow. In the present experiments, desalivated rats drank even more water while they ate "powdered" high-salt food (i.e., <15-mg food particles). The Na+ concentration of systemic plasma in these animals was not elevated during or immediately after the meal, which suggests that cerebral osmoreceptors were not involved in mediating the increased water intake. A presystemic osmoregulatory signal likely stimulated thirst because the Na+ and water contents of the gastric chyme computed to a solution approximately 150 mM NaCl. In contrast, desalivated rats drank much smaller volumes of water while eating "pulverized" high-salt food (i.e., 60-140-mg food particles), and the fluid mixture in the gastric chyme computed to approximately 280 mM NaCl solution. These and other findings suggest that the NaCl ingested in the powdered high-salt diet was dissolved in the gastric fluid and that duodenal osmoreceptors (or Na+-receptors) detected when the concentration of fluid leaving the stomach was elevated after each feeding bout, and promptly stimulated thirst, whereupon rats drank water until the gastric fluid was diluted back to isotonicity. However, when rats ate the pulverized high-salt diet, much of the NaCl ingested may have been embedded in the gastric chyme and therefore was not accessible to visceral osmoreceptors once it emptied from the stomach. Consistent with that hypothesis, fluid intakes were increased considerably when desalivated rats drank 0.10 M NaCl instead of water while eating either powdered or pulverized high-salt food.     

Gestational and early postnatal dietary NaCl levels affect NaCl intake, but not stimulated water intake, by adult rats

We examined body fluid regulation by weanling (21-25 days) and adult (>60 days) male rats that were offspring of dams fed chow containing either 0.1, 1, or 3% NaCl throughout gestation and lactation. Weanling rats were maintained on the test diets until postnatal day 30 and on standard 1% NaCl chow thereafter. Ad libitum water intake by weanlings was highest in those fed 3% NaCl and lowest in those fed 0.1% NaCl. Adult rats maintained on standard NaCl chow consumed similar amounts of water after overnight water deprivation or intravenous hypertonic NaCl (HS) infusion regardless of early NaCl condition. Moreover, baseline and HS-stimulated plasma Na(+) concentrations also were similar for the three groups. Nonetheless, adult rats in the early 3% NaCl group consumed more of 0.5 M NaCl after 10 days of dietary Na(+) deprivation than did rats in either the 1% or 0.1% NaCl group. Interestingly, whether NaCl was consumed in a concentrated solution in short-term, two-bottle tests after dietary Na(+) deprivation or in chow during ad libitum feeding, adult rats in the 3% NaCl group drank less water for each unit of NaCl consumed, whereas rats in the 0.1% NaCl group drank more water for each unit of NaCl consumed. Thus gestational and early postnatal dietary NaCl levels do not affect stimulated water intake or long-term body fluid regulation. Together with our previous studies, these results suggest that persistent changes in NaCl intake and in water intake associated with NaCl ingestion reflect short-term behavioral effects that may be attributable to differences in NaCl taste processing.     

Effects of β-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats

These experiments examined water-drinking and arterial blood pressure responses to β-adrenergic receptor activation in young (4 mo), "middle-aged" adult (12 mo), and old (29 mo) male rats of the Brown-Norway strain. We used isoproterenol to simultaneously activate β(1)- and β(2)-adrenergic receptors, salbutamol to selectively activate β(2)-adrenergic receptors, and the combination of isoproterenol and the β(2)-adrenergic receptor antagonist ICI 118,551 to stimulate only β(1)-adrenergic receptors. Animals received one of the drug treatments, and water drinking was measured for 90 min. About 1 wk later, animals received the same drug treatment for measurement of arterial blood pressure responses for 90 min. In some rats, levels of renin and aldosterone secretion in response to isoproterenol or salbutamol were measured in additional tests. Old and middle-aged rats drank significantly less after isoproterenol than did young rats and also had greater reductions in arterial blood pressure. Old and middle-aged rats drank significantly less after salbutamol than did young rats, although reductions in arterial blood pressure were equivalent across the ages. The β(2)-adrenergic antagonist ICI 118,551 abolished drinking after isoproterenol and prevented most of the observed hypotension. Renin secretion after isoproterenol and salbutamol was greater in young rats than in middle-aged rats, and wholly absent in old rats. Aldosterone secretion was reduced in old rats compared with young and middle-aged rats after treatment with isoproterenol, but not after treatment with salbutamol. In conclusion, there are age-related differences in β-adrenergic receptor-mediated drinking that can be explained only in part by age-related differences in renin secretion after β-adrenergic receptor stimulation.     

Increased cellular activity in rat insular cortex after water and salt ingestion induced by fluid depletion

Insular cortex (IC) receives inputs from multiple sensory systems, including taste, and from receptors that monitor body electrolyte and fluid balance and blood pressure. This work analyzed metabolic activity of IC cells after water and sodium ingestion induced by sodium depletion. Rats were injected with the diuretic furosemide (10 mg/kg body wt), followed 5 min later by injections of the angiotensin-converting enzyme inhibitor captopril (5 mg/kg body wt). After 90 min, some rats received water and 0.3 M NaCl to drink for 2 h while others did not. A third group had access to water and saline but was not depleted of fluids. All rats were killed for processing of brain tissue for Fos-immunoreactivity (Fos-ir). Nondepleted animals had weak-to-moderate levels of Fos-ir within subregions of IC. Fluid-depleted rats without fluid access had significantly increased Fos-ir in all areas of IC. Levels of Fos-ir were highest in fluid-depleted rats that drank water and sodium. Fos-ir levels were highest in anterior regions of IC and lowest in posterior regions of IC. These results implicate visceral, taste, and/or postingestional factors in the increased metabolic activity of cells in IC.     

Subfornical organ disconnection alters Fos expression in the lamina terminalis, supraoptic nucleus, and area postrema after intragastric hypertonic NaCl

The lamina terminalis was severed by a horizontal knife cut through the anterior commissure to determine the effects of a disconnection of the subfornical organ (SFO) on drinking and Fos-like immunoreactivity (Fos-ir) in the rat brain in response to an intragastric load of hypertonic saline (5 ml/kg of 1.5 M NaCl by gavage). After an initial load, knife-cut rats drank significantly less water than sham-cut rats, thus confirming a role for the SFO in osmotic drinking. After a second load at least 1 wk later, the rats were not allowed to drink after the gavage and were perfused for analysis of Fos-ir at 90 min. Compared with sham-cut rats, the knife-cut rats displayed significantly elevated Fos-ir in the main body of the SFO, in the dorsal cap of the organum vasculosum laminae terminalis, and in the ventral median preoptic nucleus after the hypertonic load. The knife cut significantly decreased Fos-ir in the supraoptic nucleus. Fos-ir was expressed mainly in the midcoronal and caudal parts of the area postrema of sham-cut rats, and this expression was greatly reduced in knife-cut rats. These findings strengthen the case for the presence of independently functioning osmoreceptors within the SFO and suggest that the structures of the lamina terminalis provide mutual inhibition during hypernatremia. They also demonstrate that the Fos-ir in the area postrema after intragastric osmotic loading is heavily dependent on the intact connectivity of the SFO.     

Hindbrain serotonin and the rapid induction of sodium appetite

Both systemically administered furosemide and isoproterenol produce water intake (i.e., thirst). Curiously, however, in light of the endocrine and hemodynamic effects produced by these treatments, they are remarkably ineffective in eliciting intake of hypertonic saline solutions (i.e., operationally defined as sodium appetite). Recent work indicates that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nuclei (LPBN) markedly enhance a preexisting sodium appetite. The present studies establish that a de novo sodium appetite can be induced with LPBN-methysergide treatment under experimental conditions in which only water is typically ingested. The effects of bilateral LPBN injections of methysergide were studied on the intake of water and 0. 3 M NaCl following acute (beginning 1 h after treatment) diuretic (furosemide)-induced sodium and water depletion and following subcutaneous isoproterenol treatment. With vehicle injected into the LPBN, furosemide treatment and isoproterenol injection both caused water drinking but essentially no intake of hypertonic saline. In contrast, bilateral treatment of the LPBN with methysergide induced the intake of 0.3 M NaCl after subcutaneous furosemide and isoproterenol. Water intake induced by subcutaneous furosemide or isoproterenol was not changed by LPBN-methysergide injections. The results indicate that blockade of LPBN-serotonin receptors produces a marked intake of hypertonic NaCl (i.e., a de novo sodium appetite) after furosemide treatment as well as subcutaneous isoproterenol.     

Inhibition of NaCl appetite when DOCA-treated rats drink saline

Marked increases in the consumption of concentrated NaCl solution were elicited in rats by daily injection of the synthetic mineralocorticoid, deoxycorticosterone acetate (DOCA). DOCA-treated rats drank different volumes of NaCl solution depending on its concentration (between 0.15 M and 0.50 M), with less consumed (in milliliters) the more concentrated the fluid was. In consequence, total Na(+) intake (in milliequivalents) was roughly similar in all groups. Gastric emptying of Na(+) also diminished as the concentration of the ingested NaCl solution increased, and the delivery of Na(+) to the small intestine was remarkably similar in all groups. Cumulative volume of ingested fluid in the stomach and small intestine was very closely related to intake (in milliliters) of the concentrated NaCl solutions. Systemic plasma Na(+) levels did not increase until after rats stopped consuming concentrated NaCl solution, although they were elevated at the onset of water ingestion. The situation appeared to be different when 0.15 M NaCl was consumed. This isotonic solution emptied and was absorbed relatively rapidly, and DOCA-treated rats drank larger amounts of it throughout a 1-h test period than when they drank concentrated NaCl solutions. Collectively, these findings suggest that saline consumption by DOCA-treated rats may be inhibited by two presystemic factors, one related to the volume of ingested fluid (i.e., distension of the stomach and small intestine) and one related to its concentration (i.e., elevated osmolality of fluid in the small intestine and/or in adjacent visceral tissue).     

Osmoregulatory fluid intake but not hypovolemic thirst is intact in mice lacking angiotensin

Water intakes in response to hypertonic, hypovolemic, and dehydrational stimuli were investigated in mice lacking angiotensin II as a result of deletion of the angiotensinogen gene (Agt-/- mice), and in C57BL6 wild-type (WT) mice. Baseline daily water intake in Agt-/- mice was approximately threefold that of WT mice because of a renal developmental disorder of the urinary concentrating mechanisms in Agt-/- mice. Intraperitoneal injection of hypertonic saline (0.4 and 0.8 mol/l NaCl) caused a similar dose-dependent increase in water intake in both Agt-/- and WT mice during the hour following injection. As well, Agt-/- mice drank appropriate volumes of water following water deprivation for 7 h. However, Agt-/- mice did not increase water or 0.3 mol/l NaCl intake in the 8 h following administration of a hypovolemic stimulus (30% polyethylene glycol sc), whereas WT mice increased intakes of both solutions during this time. Osmoregulatory regions of the brain [hypothalamic paraventricular and supraoptic nuclei, median preoptic nucleus, organum vasculosum of the lamina terminalis (OVLT), and subfornical organ] showed an increased number of neurons exhibiting Fos-immunoreactivity in response to intraperitoneal hypertonic NaCl in both Agt-/- mice and WT mice. Polyethylene glycol treatment increased Fos-immunoreactivity in the subfornical organ, OVLT, and supraoptic nuclei in WT mice but only increased Fos-immunoreactivity in the supraoptic nucleus in Agt-/- mice. These data show that brain angiotensin is not essential for the adequate functioning of neural pathways mediating osmoregulatory thirst. However, angiotensin II of either peripheral or central origin is probably necessary for thirst and salt appetite that results from hypovolemia.     

Serotonergic mechanisms of the lateral parabrachial nucleus and cholinergic-induced sodium appetite

Central cholinergic mechanisms are suggested to participate in osmoreceptor-induced water intake. Therefore, central injections of the cholinergic agonist carbachol usually produce water intake (i.e., thirst) and are ineffective in inducing the intake of hypertonic saline solutions (i.e., the operational definition of sodium appetite). Recent studies have indicated that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nucleus (LPBN) markedly increases salt intake in models involving the activation of the renin-angiotensin system or mineralocorticoid hormones. The present studies investigated whether sodium appetite could be induced by central cholinergic activation with carbachol (an experimental condition where only water is typically ingested) after the blockade of LPBN serotonergic mechanisms with methysergide treatment in rats. When administered intracerebroventricularly in combination with injections of vehicle into both LPBN, carbachol (4 nmol) caused water drinking but insignificant intake of hypertonic saline. In contrast, after bilateral LPBN injections of methysergide (4 microg), intracerebroventricular carbachol induced the intake of 0.3 M NaCl. Water intake stimulated by intracerebroventricular carbachol was not changed by LPBN methysergide injections. The results indicate that central cholinergic activation can induce marked intake of hypertonic NaCl if the inhibitory serotonergic mechanisms of the LPBN are attenuated.     

Inhibition of thirst when dehydrated rats drink water or saline

The present experiments sought to identify the physiological signals that inhibit thirst when dehydrated rats drink water or NaCl solution. Rats were deprived of drinking fluid but not food overnight. When allowed to drink again, the dehydrated animals consumed water or saline (0.05 M, 0.10 M, 0.15 M, or 0.20 M NaCl solution) almost continuously for 5-8 min before stopping. The volumes consumed were similar regardless of which fluid they ingested, but blood analyses indicated that increased plasma osmolality and decreased plasma volume, or both, still remained when drinking terminated. These results suggest that the composition of the ingested fluid is less significant than its volume in providing an early signal that inhibits thirst and fluid consumption by dehydrated rats. Analyses of the gastrointestinal tracts revealed that the cumulative volume in the stomach and small intestine correlated highly with the amount consumed regardless of which fluid was ingested. These and other results suggest that the volume of fluid ingested by dehydrated rats is sensed by stretch receptors detecting distension of the stomach and small intestine, which provide an early inhibitory stimulus of thirst.     

Effects of forebrain circumventricular organ ablation on drinking or salt appetite after sodium depletion or hypernatremia

In many previous studies, one or the other forebrain circumventricular organ, the subfornical organ (SFO) or organum vasculosum laminae terminalis (OVLT), was lesioned to test whether it was critical for the behavioral or physiological responses to sodium depletion and hypernatremia. These studies conflict in their conclusions. The present study was designed to create discrete lesions of both the SFO and OVLT in the same animals and to compare these with rats having a lesion of only the SFO or OVLT. Both the OVLT-lesioned group and the combined SFO + OVLT-lesioned group drank significantly more water and saline on a daily basis than Controls or SFO-lesioned rats. In both sodium depletion and hypertonic saline testing, rats with SFO lesions displayed transient deficits in salt appetite or thirst responses, whereas the rats with single OVLT lesions did not. In the sodium depletion test, but not in the hypernatremia test, rats with lesions of both the SFO and OVLT exhibited the largest deficit. The data support the hypothesis that a combined lesion eliminates redundancy and is more effective than a single lesion in sodium depletion tests. The interpretation of the OVLT lesion-only data may have been complicated by a tendency to drink more fluid on a daily basis, because some of those animals drank copious water in addition to saline even very early during the salt appetite test.     

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.