On the importance of CSF Na in the regulation of renal sodium excretion and renin release

Infusions (20 microliters/min) of isotonic (0.27 M) mannitol dissolved in Na-free artificial cerebrospinal fluid (CSF) were made for 2 h into the lateral cerebral ventricle (IVT) of conscious 68 h dehydrated sheep. The IVT infusion induced a conspicuous drop in renal sodium excretion and marked rise in plasma renin concentration (PRC). The antinatriuretic response to the IVT infusion was not altered by the intravenous administration of ADH or te converting enzyme blocker (SQ 14225, Captopril). Surgical bilateral renal denervation did not change the antinatriuretic response while the increase in PRC was extinguished. Samples of CSF were collected prior to, and 15 min after the end of the infusion. These showed a reduction in CSF [Na], while CSF osmolality remained unchanged. The study supports the view that sodium sensitive receptors close to the cerebral ventricular system participate in the regulation of renal sodium excretion and renin release, it also suggests that renal sodium excretion is affected by an unknown hormonal factor of cerebral origin, while the release of renin seen in response to a reduction in CSF [Na] is mediated by the renal nerves.     

Effect of variation of the composition of CSF in the rat upon drinking of water and hypertonic NaCl solutions

Infusing conscious unrestrained rats with either 0.5 M NaCl-CSF or 0.7 M sucrose-CSF into the lateral cerebral ventricle (IVT) at 38 microliters/hr for 4 hr induced drinking. Although the infusates were nearly equiosmotic, water drinking during the 0.5 M NaCl-CSF was greater than during 0.7 M sucrose-CSF. However, IVT infusions of 0.7 M mannitol-CSF at rates of 9.4 microliters/hr or 38 microliters/hr for 4 hr or 10 microliters/hr for 4 days failed to induce water drinking. Also, IVT infusion of 0.27 M mannitol-CSF at 38 microliters/hr for 4 hr failed to significantly alter water drinking. CSF [Na] was reduced by IVT infusion of either 0.7 M sucrose-CSF or 0.7 M mannitol-CSF. In contrast, CSF [Na] was increased by 4-hr IVT infusion of 0.5 M NaCl in rats denied access to water during the infusion. Intake of 0.5 M NaCl was not altered significantly from control intakes by any of the above IVT infusions. It is concluded that water drinking in the rat may be initiated by stimulation of either a sodium sensitive sensor alone or with an osmoreceptor system and that species specific differences in the induction of both water drinking and hypertonic saline drinking are apparent.     

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.     

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.     

Transient vasopressin release and thirst in response to prolonged intracerebroventricular infusions of hypertonic mannitol in saline

In the conscious goat infusions of 0.4 M mannitol in 0.15 M NaCl into the lateral cerebral ventricle (40 or 100 min, 0.02 ml/min) caused slight, transient vasopressin release and temporary thirst, whereas infusions or pure, hypertonic (0.7 M) mannitol did not elicit thirst and inhibited the basic vasopressin release in the nonhydrated animal. In contrast, infusions of equiosmolal (0.35 M) NaCl induced persistent thirst and pronounced elevation of the plasma vasopressin concentration throughout the infusion period. The cerebrospinal fluid (CSF) osmolality was raised by the same order of magnitude (= 13%) after the mannitol/NaCl and the hypertonic NaCl infusions. The CSF Na+ concentration was elevated by greater than 10% at 5 min after hypertonic NaCl infusions, but it was reduced by approximately 10% at 5 min after the mannitol/NaCl infusions. There was no appreciable difference in the CSF K+ concentration after the infusions. The results are discussed with regard to the possible importance of CSF Na+-concentration as opposed to strict osmotic factors for the excitation of receptors involved in the control of water balance.     

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)     

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.     

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.     

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.     

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.     

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.     

Reducing brain sodium concentration prevents post-prandial and dehydration-induced natriuresis in sheep

Renal Na excretion during the 24 h following feeding was studied in sheep. A pronounced natriuresis occured 3.5-5.5 h after feeding. Na excretion then fell to low levels in animals allowed to drink water, but was significantly elevated above this level in water-deprived sheep for most of the remaining period. Both the post-prandial and dehydration-induced natriuresis were prevented by intracerebroventricular (icv) infusions of low Na concentration 0.3 mol 1^-1 mannitol at 1 ml h^_1, and a water diuresis also occurred. These effects were not caused by icv infusion of artificial cerebrospinal fluid (Na concentration = 150 mmol l^-1). As a result, there was a much greater increase in plasma Na concentration and osmolality in the sheep given icv mannitol. Intravenous infusion of vasopressin prevented the water diuresis induced by icv mannitol, but the inhibition of natriuresis was still observed and plasma Na concentration increased by 8 mmol l^-1 over 24 h compared with an increase of 3 mmol l^-1 in dehydrated sheep infused icv with artificial cerebrospinal fluid. The results show that the ambient Na concentration in the brain plays an important role in the normal homeostatic regulation of Na balance by the kidney in sheep.     

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].     

A central osmosensitive receptor for renal sodium excretion.

1. The effect on renal Na and water excretion of increasing the NaCl concentration of blood supplying the brain was investigated in conscious water-loaded sheep. Intracarotid infusion ot 4 M-NACl at 0-8 ml./min for 60 min was compared with equivalent intrajugular infusion. 2. A more rapid increase in renal Na excretion and urine osmolality occurred with the intracarotid infusions than with intrajugular infusions. 3. Intracarotid infusions of 2 M sucrose or fructose at 1-6 ml./min for greater increase in renal Na excretion, urine osmolality and a decrease in urine flow rate. 4. The results suggest that there are receptors in the brain sensitive to changes in extracellular tonicity which influence renal Na excretion. It is possible that changes in ADH secretion alone mediate the early natriuresis seen with intracarotid hypertonic infusions although an alternative concurrent mechanism cannot be ruled out.     

Search for a natriuretic mechanism sensitive to sodium in the brain of the monkey.

1. The effects of hypertonic saline infusion into the third ventricle were investigated in ten monkeys which were pre-operated, trained, and used in the conscious state under controlled conditions. 2. In non-hydrated monkeys, intraventricular infusion of NaCl 1.0 M, 0.01 ml./min for 30 min did not affect urine volume or Na output but produced a small increase in urine osmolality. Comparable infusion of NaCl 0.15 M had no effect on any parameter. 3. In monkeys undergoing water diuresis (with i.v. infusion of 5% dextrose), intraventricular hypertonic saline produced large reciprocal changes in urine volume and osmolality while urine Na showed no significant change. The effects on urine volume and osmolality were greater than those of lysine-vasopressin 30 m-u./kg i.v. 4. The absence of natriuresis after intraventricular hypertonic saline infusion in the monkey was in notable contrast to the results reported in lower species. However, the data suggested that the infusion probably released ADH as in other species.     

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.     

Cerebral osmoregulatory reduction of plasma renin concentration in sheep

A centrally mediated inhibitory influence of plasma hypertonicity on renin secretion was investigated in conscious, Na-depleted sheep. Infusions of hypertonic solutions were made into the carotid artery or jugular vein, and the effects on plasma renin concentration (PRC) compared. Intracarotid infusion of 1.65 M NaCl significantly reduced PRC (to 74% of the pre-infusion value) within 15 min of the commencement of the infusion whereas corresponding intrajugular infusion did not. Intracarotid infusion of 3 M sorbitol for 45 min also reduced PRC (to 64% of the pre-infusion level) significantly after 15 min of infusion. By contrast, neither intrajugular infusion of 3 M sorbitol, nor intracarotid infusion of isotonic 0.15 M NaCl for 45 min significantly reduced PRC. Intracarotid infusion of hypertonic sorbitol for 45 min did not inhibit PRC in sheep with cerebral lesions of the lamina terminalis. These results show that plasma hypertonicity may have an inhibitory influence on renin secretion. The inhibition is probably mediated by an effect of hypertonicity on the CNS, rather than a direct effect on the kidney.     

Mannitol-induced hyperosmolality and cerebrospinal fluid vasopressin in anesthetized cats

Arginine-vasopressin (AVP) has been found to influence brain water. Since AVP is released by hyperosmolality into plasma we determined the role of AVP in controlling cerebrospinal fluid (CSF) pressure. Adult cats were anesthetized with pentobarbital and samples of plasma and cisternal CSF were collected 1 or 2 h before i.v. infusion of 2 g/kg of mannitol and for 2 h afterwards. We found a significant increase in plasma osmolality from 320.0 +/- 1.6 to 331.6 +/- -3.4 mOsm/l (mean +/- S.E.M.), while CSF osmolality was unchanged. Prior to mannitol infusion, AVP was elevated to 105 +/- 19 pg/ml in plasma and to 136 +/- 19 pg/ml (mean +/- S.E.M.) in CSF. After infusion of mannitol AVP levels were unchanged in either plasma or CSF. The reduction of CSF pressure by mannitol is independent of AVP in the anesthetized cat.     

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)     

Effects of osmotic gradients on water and solute transport: in vivo studies in rat duodenum and ileum.

We examined effects of luminal osmolality on net water and solute movements in rat duodenum and ileum. Solutions of sodium chloride (permeating solute) or mannitol (nonpermeating solute) at hypo-, iso-, or hyperosmotic concentrations were recirculated through in situ segments. Luminal osmolality increased towards that of plasma with hyposmotic solutions of both solutes. With isosmotic solutions, luminal osmolality did not change with sodium chloride, but increased with mannitol. With hyperosmotic solutions, luminal osmolality always decreased toward that of plasma with sodium chloride; with mannitol, however, decreases were significant only when initial concentrations were above 400 mosmol/kg. The decrease in osmolality of hyperosmotic sodium chloride resulted from sodium absorption and water secretion. Thus, both hypo- and hyperosmotic solutions of sodium chloride adjusted toward isomolality with plasma by the usual mechanisms of water and solute movement. With mannitol, however, osmotic adjustment of hypertonic luminal contents was restricted or even absent due to movement of sodium down its concentration gradient and reduced hydraulic conductivity of the gut.