Osmoreceptor mechanism for oxytocin release in the rat

In order to determine whether oxytocin release is controlled by an osmoreceptor mechanism identical with that for vasopressin release, the plasma oxytocin concentration and plasma osmolality were measured during intraatrial infusion and after intraventricular injection of various osmotic solutions in unanesthetized rats. Intraatrial infusion of 0.6 M NaCl Locke solution (L.S.) or 1.2 M mannitol L.S. elevated plasma oxytocin significantly, while 1.2 M urea L.S. caused only a small increase and isotonic L.S. did not change in plasma oxytocin. All hypertonic solutions produced significant and similar increases in the plasma osmolality. Plasma oxytocin was positively correlated with plasma osmolality in the animals infused with hypertonic NaCl or mannitol but not in the animals infused with hypertonic urea. The injection of 2 microliters of 0.6 M NaCl artificial cerebrospinal fluid (CSF) or 1.2 M mannitol CSF into the third ventricle caused a significant increase in plasma oxytocin immediately (5 min after injection) without changing plasma osmolality, while the intraventricular injection of 1.2 M urea CSF or isotonic CSF produced no significant change in plasma oxytocin. These results indicate that oxytocin release is controlled by osmoreceptors rather than Na receptors, that the adequate stimulus for the osmoreceptors is one which produces cellular dehydration and that the osmoreceptors are located in the brain region which is accessible to osmotic agents from both the outside and inside of the blood-brain barrier. Since the organum vasculosum of the lamina terminalis (OVLT) lacks a blood-brain barrier and is known to be involved in osmotic control of vasopressin release, a lesion was made in the anteroventral region of the third ventricle which encompasses the OVLT and the effect of hypertonic NaCl infusion on oxytocin release was examined. No significant increase in plasma oxytocin was observed after intraatrial infusion of 0.6 M NaCl L.S. in the lesioned rats. All of these findings lead to the conclusion that oxytocin release is under the control of osmoreceptors identical to those for vasopressin release.     

Dipsogenic Effects of Intracarotid Infusions of Various Hyperosmolal Solutions

Thirst in response to intracarotid and intravenous infusions (1.5 ml/min) of various hypertonic, equi-osmolal solutions was studied in the goat. Intracarotid infusions of 1 M NaCl and of 2 M fructose induced conspicuous cumulative drinking. The amount of water drunk during intracarotid infusions of 2 M urea and glycerol was only about a third of that consumed during the corresponding infusions of NaCl and fructose. During intracarotid infusions of 2 M galactose and glucose drinking was inconsistent. Of the intravenous infusions only hypertonic NaCl had a consistent dipsogenic effect. However, the amount of water consumed was considerably smaller and the latency time for drinking much longer than during the intracarotid infusions of NaCI. It is concluded that intracarotid infusions of hypertonic solutions act as considerably stronger thirst stimuli than corresponding intravenous infusions, and that the most pronounced dipsogenic effect is obtained by intracarotid infusions of those hypertonic solutions which also most effectively release antidiuretic hormone in the hydrated goat. The possibility is discussed that intracarotid infusions may stimulate the thirst mechanism indirectly via a rise in the Na+ concentration of the cerebrospinal fluid.     

The dipsogenic effect of intracerebroventricular infusion of hypertonic NaCl in the sheep is mediated mainly by the Na ion

In order to examine the importance of the chloride ion in the dipsogenic effect of intracerebroventricular (ICV) infusion of hypertonic NaCl, the water intake in response to 30-min ICV infusions of hypertonic solutions of different Na salts (0.25 M NaCl, NaI, NaSCN and 0.125 M Na2S2O3), mannitol (0.5 M) and choline chloride (0.25 M) was studied in the sheep. All solutions of the Na salts caused significant water drinking compared with ICV control infusions of isotonic artificial cerebrospinal fluid (CSF), except Na thiosulphate (Na2S2O3), which was much less effective, even after equilibration of its osmolality with the other sodium solutions by adding mannitol (0.125 M Na2S2O3/0.25 M mannitol). An inconsistent and small intake of water was induced by ICV hypertonic mannitol and choline chloride. It is concluded that the dipsogenic effect of ICV infusion of hypertonic NaCl in the sheep is mainly caused by the increased Na rather than the Cl ion concentration or the hyperosmolality in the extracellular fluid of juxtaventricular brain tissue.     

Water drinking caused by intracerebroventricular infusions of hypertonic solutions in cattle

Infusions into the lateral cerebral ventricle of hypertonic solutions of NaCl, mannitol or sucrose all induced water drinking in cattle. However, infusion of hypertonic NaCl caused a significantly greater water drinking response than did the infusions of mannitol or sucrose, despite the fact that CSF osmolality increase was similar. In contrast, hypertonic solutions of NaCl or mannitol had similar dipsogenic effects when infused intravenously. The intracerebroventricular infusions of hypertonic NaCl or mannitol did not affect the intakes of food or Na solution. The results are consistent with the hypothesis that both cerebral osmoreceptors and Na sensors are involved in regulating thirst in cows.     

Influence of mannitol-induced reduction in CSF Na on nervous and endocrine mechanisms involved in the control of fluid balance

Infusions (20 μl/min) of isotonic (0.27 M) and hypertonic (0.7 M) mannitol dissolved in Na-free artificial CSF were made for 1 h. into the lateral cerebral ventricle (IVT) of conscious water-replete sheep. The IVT infusion of both 0.27 M and 0.7 M mannitol induced a water-diuresis. Samples of CSF were collected prior to, and 5, 35, 65 and 125 min after the end of the infusion. These consistently showed a reduction in CSF [Na], while CSF osmolality remained unchanged after 0.27 M mannitol, and was considerably increased after 0.7 M mannitol. In the 44 h dehydrated sheep IVT infusion of 0.7 mannitol in Na-free artificial CSF was made for 6 h. The water deprivation as such caused a marked increase in plasma and CSF [Na] and osmolality. The 6 h IVT infusion of hypertonic mannitol further increased the CSF osmolality, while CSF [Na] decreased and reached a value below the normal for water-replete animals. The infusion also induced a fall in plasma ADH resulting in a water-diuresis, and extinguished the thirst of the dehydrated sheep. Furthermore, the infusion markedly reduced renal sodium excretion without causing any substantial change in blood aldosterone, in spite of the fact that there was a conspicuous increase in plasma renin concentration. The study supports the view that sodium sensitive receptors close to the cerebral ventricular system participate in the regulation of ADH secretion, water intake, renin release, and renal sodium excretion.     

Lowered cerebrospinal fluid sodium antagonizes effect of raised blood sodium on salt appetite

Moderately Na-deficient sheep (i.e., Na deficit = 300-400 mmol) will correct their deficit when given hypertonic NaHCO3 solution to drink. Access to NaHCO3 was provided by bar press for 2 h only each day following 22 h of salivary loss from a parotid fistula. Each delivery by bar press provided 9 mmol of NaHCO3 and, of the 46.3 +/- 2.5 deliveries made and drunk in 2 h, 80-90% were made in the first 20 min. Ten minutes before access to NaHCO3 commenced an intracarotid infusion of 4 M NaCl at 1.6 ml/min for 30 min was initiated. This infusion reduced intake by approximately 80% and increased both plasma and cerebrospinal fluid sodium concentration (CSF[Na]). Intraventricular (ivt) infusion of 0.7 M mannitol in artificial CSF at 1 ml/h for 3 h begun 1 h before access to Na by bar press lowered CSF[Na] and approximately doubled voluntary Na intake. The combination of the two procedures resulted in NaHCO3 intake similar to base line. That is, the ivt infusion of 0.7 M mannitol counteracted the inhibition of Na appetite produced by the systemic infusion of hypertonic NaCl, and this was associated with attenuation of the effect of the systemic 4 M NaCl infusion on CSF[Na]. The results suggest that the effects of both the ivt and the systemic infusions are mediated via the same sensor system located within the neuropil.     

Water intake and changes in plasma and CSF composition in response to acute administration of hypertonic NaCl and water deprivation in sheep

Water intake and changes in plasma and cerebrospinal fluid (CSF) composition were measured in response to intracerebroventricular (i.c.v.) and intracarotid infusions of hypertonic NaCl solutions and after 48 h of water deprivation in sheep. Significant interindividual differences in dipsogenic sensitivity to i.c.v. NaCl were found, whereas no such differences were observed in response to intracarotid infusion of hypertonic NaCl. In the more sensitive animals, the increase in CSF [Na] at initiation of drinking during i.c.v. infusion did not differ significantly from the increase in plasma [Na] seen at the thirst threshold during intracarotid infusion of 1 M NaCl. The thirst-eliciting infusions of hypertonic NaCl into the carotid arteries were associated with a small, significant, increase in CSF [Na], which however did not differ from that caused by an i.c.v. non-dipsogenic 'control' infusion of a slightly hypertonic (0.154 M) NaCl solution. Water deprivation for 48 h induced increases in CSF and plasma [Na] similar to those observed at the onset of drinking in response to i.c.v. and intracarotid infusions of hypertonic NaCl. However, the dehydrated animals drank about four times the amount of water consumed in response to the separate treatments with hypertonic NaCl. It is concluded that significant interindividual differences in dipsogenic sensitivity to osmotic stimuli are present in sheep, and that these differences may not necessarily be simultaneously expressed on both sides of the blood-brain barrier. The thirst-eliciting effect of intravascular infusion of hypertonic NaCl may be induced without concomitant increase in CSF [Na] and/or osmolality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interaction of changes in the third ventricular CSF tonicity, central and systemic AVP concentrations and water intake

Arginine vasopressin (AVP) is assumed to be involved as a central transmitter or modulator in the control of autonomic functions including thirst. In conscious dogs AVP concentration in cerebrospinal fluid (CSF) from the anterior part of the third ventricle (A3V) was analysed before and after local elevation of CSF osmolality by intracerebroventricular (i.c.v.) infusion of 0.35 M NaCl and after i.c.v. AVP infusion at 46 and 138 fmol ml-1 for 10 min. In addition, the effects of these i.c.v. infusions on water intake, plasma AVP concentration and blood pressure were investigated. In euhydrated dogs 0.35 M NaCl i.c.v. did not alter AVP concentration in the CSF during the subsequent 2 h. In contrast, plasma AVP concentration had increased significantly from 3.4 +/- 0.3 (control) to 6.4 +/- 0.7 and 4.7 +/- 0.3 fmol ml-1, 4 and 16 min, respectively, after the hypertonic stimulus. Drinking was stimulated with an average water intake of 14.5 +/- 3.7 ml kg-1 body wt. However, AVP infusion into the A3V did not elicit water intake despite increases of AVP concentration in the A3V by factors up to 40 above control. The same animals responded with spontaneous drinking to 0.35 M NaCl i.c.v. administered 160 min after the end of AVP infusions. Exogenously administered AVP disappeared from the A3V with a time constant of 13.8 min. The results do not support the view that AVP in the A3V CSF per se stimulates drinking.     

The influence of intracerebroventricular infusions on osmotically induced urine excretion in the pigeon (Columba livia)

This study deals with the influence of intracerebroventricular (ICV) infusions on urine volume and electrolyte excretion in response to a peripherally administered osmotic load in conscious behaving pigeons. The ICV infusions were intended to influence the cerebrospinal fluid (CSF) sodium (Na+) concentration that would have been increased by the hypertonic NaCl or sucrose solutions infused intravenously (IV). Urine and electrolyte excretion following IV infusion of 0.5 M NaCl were enhanced by simultaneous ICV infusion of 0.3 M NaCl and essentially unchanged by ICV infusions of 0.3 M or 0.9 M sucrose, or water. Infusions (ICV) of water, isotonic and hypertonic NaCl or sucrose did not significantly influence urine and electrolyte excretions following IV infusion of 1.0 M NaCl or sucrose (except K+ in the case of ICV/IV sucrose). Isotonic (0.3 M) or hypertonic (0.9 M) sucrose infused ICV enhanced urine and electrolyte excretion following IV infusion of 1.5 M sucrose. Similar amounts of sodium were excreted following IV infusion of 0.5 M NaCl, 1.0 M sucrose or 1.5 M sucrose plus the ICV infusions. The results suggest that the concentration of Na+ in the CSF is one of the factors that play a role in urine and electrolyte excretion following IV administration of osmotic stimuli in the pigeon.     

Duration of central action of angiotensin II estimated by its interaction with csf Na+.

In pre-hydrated goats, an urge to drink persisted for approximately half an hour after combined infusions of angiotensin II and hypertonic (0.5 M) NaCl into the lateral or third cerebral ventricle. The intraventricular infusion of angiotensin/glucose solution, having no dipsogenic action of its own, markedly accentuated the dipsogenic and antidiuretic effects of the subsequent intraventricular infusion of hypertonic NaCl. The possibility is discussed that angiotensin may be bound at periventricular receptor sites where it continues to interact with Na+ in eliciting thirst and ADH release for about half an hour.     

Extracellular hyperosmolality and body temperature during physical exercise in dogs

The purpose of this study was to test the hypothesis that thermoregulation during exercise can be affected by extracellular fluid hyperosmolality [Osm] without changing the plasma Na+ concentration. The effects of preexercise venous infusions of hypertonic mannitol and NaCl solutions on rectal temperature (Tre) responses were compared in dogs running at moderate intensity for 60 min on a treadmill. Plasma E1Na+] was increased by 12 meq/l (P less than 0.05) after NaCl infusion, and decreased by 9 meq/l (P less than 0.05) after mannitol infusion. Both infusions increased plasma [Osm] by 15 mosmol/kg (P less than 0.05). After both infusions, Tre was essentially constant during 60 min rest. However, compared with the noninfusion exercise increase in Tre of 1.3 degrees C, Tre increased by 1.9 degrees C (delta delta Tre = 0.5 degrees C, P less than 0.05) after both postinfusion exercise experiments. It was concluded that inducing extracellular hyperosmolality, without elevating plasma [Na+], can induce excessive increases in Tre during exercise but not at rest.     

Evidence for cerebral sodium sensors involved in water drinking in sheep

Evidence supporting cerebral Na sensors in the initiation of thirst is the greater water drinking which occurs with intracerebroventricular (ICV) infusion of hypertonic NaCl than with ICV hypertonic saccharide solution. However, ICV infusion of hypertonic saccharide solution causes a reduction in CSF [Na], even though the saccharide is made in solution with normal [Na] of 150 mM. To prevent this, ICV infusion of hypertonic sucrose in high Na solution was made. The ICV infusion of 0.3 M sucrose/0.3 M NaCl-CSF caused water intake of 416 ± 173 ml (mean ± SEM) in 6 sheep, and CSF [Na] was 151 ± 0.9 mM, but ICV infusion of equiosmolar 0.45 M NaCl-CSF caused greater water intake of 1097 ± 202 ml and CSF [Na] increased to 178.8 ± 3.6 mM. Control ICV isotonic CSF did not cause drinking and CSF [Na] was 150.5 ± 0.8 mM whereas ICV 0.6 M sucrose-CSF ([Na]=150 mM) caused water intake of 132 ± 63 ml with CSF [Na] falling to 139.3 ± 1.3 mM. These results indicate specific brain NaCl sensors involved in thirst. Osmoreceptors may also exist because some drinking occurred with ICV sucrose despite reduced CSF [Na].     

Effects of ethanol ingestion on thirst and fluid consumption in humans

To investigate the effects of ethanol on thirst, fluid intake was measured in 24 normal subjects for 3 h after consumption of 1.0 g/kg ethanol, with or without administration of a vasopressin analogue (DDAVP) before ethanol ingestion. Fluid consumption was reduced in subjects receiving DDAVP, suggesting that thirst after ethanol is largely secondary to dehydration due to inhibition of vasopressin release. Further, the effects of ethanol on salt-load-elicited thirst and fluid consumption in normal subjects were studied using intravenous hypertonic saline infusions. Subjects acted as their own controls and received 0.5 or 1.0 ml/kg ethanol 30 min before infusions on one day and an equal volume of fluid on another day. During infusions after ethanol, subjects experienced thirst later and at higher osmolalities. They also drank less immediately after infusions with prior ethanol ingestion. The relationship between thirst score and plasma osmolality was shifted to higher osmolalities by ethanol. Thus, although ethanol progressively causes thirst secondary to dehydration, it has a direct inhibitory effect on the thirst response to osmotic stimulation.     

Inhibition of vasopressin-release during developing hypernatremia and plasma hyperosmolality: an effect of intracerebroventricular glycerol

In non-hydrated goats prolonged (3 h, 0.02 ml/min) intracerebroventricular (IVT) infusion of 0.35 M glycerol depressed the plasma vasopressin level during the entire infusion period which resulted in a conspicuous water diuresis outlasting the infusion by about 20 min. Since no compensatory drinking occurred during this sustained water diuresis it gradually induced pronounced dehydration (loss of greater than 1 liter of total body water causing 5% increase in plasma [Na+] and osmolality). The same degree of dehydration was in other experiments induced by water deprivation. It then caused a 5-fold increase in plasma vasopressin level. Corresponding IVT infusions of 0.35 M d-glucose depressed plasma vasopressin level only during the first half of the 3 h infusion period. Consequently, the resulting water diuresis was transient and subsided before the glucose infusion was finished. Plasma renin activity increased during the IVT glycerol infusion and during water deprivation, but was largely unaffected by IVT glucose. Both IVT glycerol and glucose decreased renal sodium excretion. The possibility is discussed that the pronounced ability of IVT glycerol to depress the vasopressin release and thirst is not only due to dilution induced reduction of CSF [Na+], but also to an influence of glycerol on choroidal and/or transependymal Na+-transporting mechanisms.     

Increased resistance to haemorrhage induced by intracerebroventricular infusion of hypertonic NaCl in conscious sheep.

The effect of elevated cerebrospinal fluid Na+ concentration (CSF [Na+]) on the tolerance of blood loss, and concomitant cardiovascular and humoral responses were studied in conscious sheep. A slow (0.7 ml kg-1 min-1) venous haemorrhage was continued until the mean systemic arterial pressure suddenly decreased to less than 50 mmHg, or in the absence of hypotension, until a total blood loss of 25 ml kg-1. Significantly more blood had to be removed to induce hypotension in animals receiving an intracerebroventricular (i.c.v.) infusion (0.02 ml min-1) of 0.5 M NaCl (starting 30 min before haemorrhage and continued throughout the experiment) compared to control haemorrhages without concomitant i.c.v. infusion (22.7 +/- 1.2 ml vs 16.9 +/- 0.9 ml kg-1). In one animal, subjected to 0.5 M NaCl infusion, the blood pressure was still maintained at 25 ml kg-1 of haemorrhage. In spite of a larger blood loss, animals receiving i.c.v. infusion of hypertonic NaCl had an improved recovery of the blood pressure after haemorrhage, due to a better maintained cardiac output rather than to a reinforced increase of the vascular resistance. The improved cardiovascular responses to haemorrhage during elevated CSF [Na+] are not readily explained by the effects on the plasma concentrations of vasopressin, angiotensin II or noradrenaline, although the latter was augmented. The plasma protein concentration decreased already during the 30 min of hypertonic NaCl infusion preceding haemorrhage, and the haemodilution caused by the subsequent blood removal was aggravated, which indicates that this treatment also causes transfer of fluid to the plasma compartment. We conclude that elevated CSF [Na+] increases tolerance to haemorrhage and improves cardiovascular function after blood loss in sheep. Since the haemodynamic responses in many respects were similar to those reported in response to the systemic administration of a small volume of hypertonic NaCl solution in haemorrhagic shock, part of the effect of that treatment may be mediated via cerebral effects of increased Na+ concentration.     

Water intake and changes in plasma and CSF composition in response to acute administration of hypertonic NaCI and water deprivation in sheep

Water intake and changes in plasma and cerebrospinal fluid (CSF) composition were measured in response to intracerebroventricular (i. e.v.) and intracarotid infusions of hypertonic NaCI solutions and after 48 h of water deprivation in sheep. Significant interindividual differences in dipsogenic sensitivity to i. e.v. NaCI were found, whereas no such differences were observed in response to intracarotid infusion of hypertonic NaCI. In the more sensitive animals, the increase in CSF [Na] at initiation of drinking during i. e.v. infusion did not differ significantly from the increase in plasma [Na] seen at the thirst threshold during intracarotid infusion of 1 M NaCI. The thirst-eliciting infusions of hypertonic NaCI into the carotid arteries were associated with a small, significant, increase in CSF [Na], which however did not differ from that caused by an i. e. v. non-dipsogenic ‘control’ infusion of a slightly hypertonic (0.154 _M) NaCI solution. Water deprivation for 48 h induced increases in CSF and plasma [Na] similar to those observed at the onset of drinking in response to i. e.v. and intracarotid infusions of hypertonic NaCI. However, the dehydrated animals drank about four times the amount of water consumed in response to the separate treatments with hypertonic NaCI. It is concluded that significant interindividual differences in dipsogenic sensitivity to osmotic stimuli are present in sheep, and that these differences may not necessarily be simultaneously expressed on both sides of the blood-brain barrier. The thirst-eliciting effect of intravascular infusion of hypertonic NaCI may be induced without concomitant increase in CSF [Na] and/or osmolality. A simultaneous increase in CSF and plasma [Na] and/or osmolality is suggested to contribute to the conspicuous water consumption seen in response to dehydration compared to that caused by acute administration of hypertonic NaCl.     

Changes in sodium appetite in cattle induced by changes in CSF sodium concentration and osmolality

Alteration of the sodium concentration in the cerebrospinal fluid (CSF) of sheep induces reciprocal changes in sodium appetite. Similar studies have now been performed in cattle. Heifers were prepared with a unilateral parotid fistula and guide tubes were implanted in the skull for the introduction of probes into the lateral ventricles in order to sample CSF and infuse artificial CSF solutions. The cows were Na depleted by loss of saliva for 46 hr and then given free access for 2 hr to 300 mM NaCl/NaHCO3 solution. Artificial CSF infusions at 1.9 ml/hr were begun one hour before Na access. In control experiments, the cows drank 26.4 +/- 1.2 l of Na solution in 2 hr, 1.2 +/- 0.2 l of water in the preceding hour, and 0.3 +/- 0.1 l of water during Na access. Sham or standard isotonic CSF infusions did not alter these values. CSF [Na+] rose from approximately 142 to approximately 148 mmol/l, attributable to the effects of drinking the large volume of hypertonic Na solution. Infusion of 500 mM NaCl CSF increased CSF [Na+] and reduced Na intake and increased water intake. Infusion of 700 mM mannitol: 150 mM NaCl CSF reduced CSF [Na+] and increased both Na and water intake. Infusion of a mixture of these solutions had no effect on CSF [Na+] and increased water intake only. Infusion of 270 mM mannitol CSF reduced CSF [Na+] and slightly reduced Na intake. Standard isotonic CSF containing 0.5 or 2.0 micrograms/ml of angiotensin II increased water intake only.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hypertonic intracarotid infusions on plasma vasopressin concentration

The effect of short-term bilateral intracarotid infusions of hypertonic saline on plasma vasopressin concentration (pAVP) was evaluated in five dogs. Intracarotid infusion of saline at 90 mumol . kg-1 . min-1 . artery-1 significantly (P less than 0.05) increased jugular vein osmolality (pOsm) and sodium concentration (pNa+) within 2 min. Saphenous vein pOsm was not altered during the 6 min of infusion, whereas pNa+ was increased (P less than 0.05) from 0.8 +/- 0.1 to 2.3 +/- 0.3 pg/ml. Subsequent experiments using hypertonic saline infusions of 90 and 180 mumol . kg-1 . min-1 administered intracarotidly and intravenously for 6 min were performed. Intracarotid isotonic infusions and intravenous hypertonic infusions did not significantly alter pAVP. Hypertonic intracarotid saline increased jugular vein pOsm and pNa+ in a dose-related fashion, whereas saphenous vein pOsm and pNa+ were not significantly changed after 6 min of infusion. Plasma vasopressin, compared with the isotonic intracarotid infusion (1.5 +/- 0.3 pg/ml), was increased (P less than 0.05) after hypertonic saline to 3.2 +/- 0.6 and 4.8 +/- 0.2 pg/ml for the 90 and 180 mumol . kg-1 . min-1 infusions, respectively. The cerebral osmolality indicated by jugular vein pOsm was therefore increased in the absence of changes in systemic pOsm during intracarotid hypertonic infusions. The increase in pAVP in response to these changes in pOsm supports the presence of central osmoreceptors regulating vasopressin release in the area of distribution of the common carotid arteries.     

The dipsogenic effect of intracerebroventricular infusion of hypertonic NaCI in the sheep is mediated mainly by the Na ion

In order to examine the importance of the chloride ion in the dipsogenic effect of intracerebroventricular (ICV) infusion of hypertonic NaCI, the water intake in response to 30-min ICV infusons of hypertonic solutions of different Na salts (0.25 M NaCI, Nal, NaSCN and 0.125 _M Na₂S₂O₃), mannitol (0.5 M) and choline chloride (0.25 M) was studied in the sheep. All solutions of the Na salts caused significant water drinking compared with ICV control infusions of isotonic artificial cerebrospinal fluid (CSF), except Na thiosulphate (Na₂S₂O₃), which was much less effective, even after equilibration of its osmolality with the other sodium solutions by adding mannitol (0.125 M Na₂S₂O₃/o.25 M mannitol). An inconsistent and small intake of water was induced by ICV hypertonic mannitol and choline chloride. It is concluded that the dipsogenic effect of ICV infusion of hypertonic NaCI in the sheep is mainly caused by the increased Na rather than the CI ion concentration or the hyperosmolality in the extracellular fluid of juxtaventricular brain tissue.     

Separate mechanisms for central osmotically-induced drinking and vasopressin release in minipigs

Operant drinking and lysine vasopressin (LVP) release were investigated in minipigs following intracerebroventricular (ICV) injections of hypertonic equiosmolar (1.4 osM) solutions of NaCl and of sucrose and mannitol dissolved in 0.15 M NaCl or water, and of urea dissolved in 0.15 M NaCl. Hypertonic (0.74 M) NaCl produced significant drinking and LVP release in all minipigs tested whereas hypertonic equiosmolar (1.4 osM) solutions of sucrose and mannitol induced only drinking. Mannitol, both with and without NaCl, was more effective than sucrose. Hypertonic urea was ineffective both as an osmotic dipsogen and at stimulating the release of LVP. These results suggest that two independent mechanisms could be involved in drinking and LVP responses to ICV administration of hypertonic solutions in minipigs.