Fall In Plasma Osmolality Research Articles

Extracellular hydration, cardiovascular risk, and the interstitium: a three-dimensional view

Volume expansion is a major contributor to poor cardiovascular outcomes in kidney disease. The relationship of extracellular volume (ECV) overload to cardiovascular changes in chronic kidney disease (CKD) remains speculative. Recent studies are challenging traditional concepts and providing new insight into mechanisms and the relationship of ECV to cardiovascular health. A dynamic role of the extracellular interstitium in inducing cardiovascular risk is emerging in CKD.

Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies

Investigations in the rat model of pregnancy indicate an important role for the corpus luteal (CL) hormone relaxin in the maternal circulatory and osmoregulatory changes in pregnancy, which are epitomized by profound vasodilation and modest hypoosmolality, respectively. In a pilot study of infertile women who became pregnant through donor eggs, in vitro fertilization, and embryo transfer, the gestational rise in glomerular filtration and fall in plasma osmolality were markedly subdued. Because these women were infertile, they lacked a CL and circulating relaxin (and possibly other vasoactive CL hormones). Based on these findings in pregnant rats and women, we hypothesize that infertile women conceiving through donor eggs will have overall subdued circulatory changes (e.g., attenuated reduction in systemic vascular resistance and subdued increase in cardiac output) particularly during early pregnancy when CL hormones predominate before the full development and maturation of the placenta. In contrast, infertile women conceiving by autologous eggs retrieved after ovarian stimulation and fresh embryo transfer may have a relatively hyperdynamic circulation due to the presence of many CL (up to 20 or more) and higher circulating levels of vasodilatory ovarian hormones such as relaxin. Emerging evidence suggests that women undergoing Assisted Reproductive Technologies (ART) have increased risk for adverse pregnancy outcomes such as preeclampsia and small for gestational-age babies. This increased risk may be partly caused by the maternal milieu, which is not physiological in ART pregnancies due to the abnormal status of the CL.

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Thirst Perception And Drinking In Euhydrate And Dehydrate Human Subjects

Studies on how the body senses the need to correct extracellular and intracellular volumes and ionic concentration changes is relatively scanty. The present studies were designed to determine the effect of oral distilled water (DW) and saline loads, gargling with DW and DW preload on thirst perception (TP) and drinking in euhydrate and dehydrated subjects. The subjects were healthy male volunteers between the ages of 17 and 35 years. Group A subjects were given DW or various concentrations of sodium chloride [NaCl] orally. Subjects in groups B, C and D were dehydrated for 18 hours before the experiment. Group B gargled 500 ml of DW in divided volume of 50 ml at five minutes interval over a period of 50 minutes. Group C gargled with DW and different concentrations of NaCl. Group D were preloaded with four volumes of DW before ad libitum DW intake. TP was rated using the Visual Analogue Scale. Results showed that in Group A, drinking DW reduced TP, suggesting that baseline TP in normal euhydrate subjects is slightly elevated. Drinking DW reduced TP more than drinking NaCl solutions. Gargling resulted in a gradual fall in TP. The decrease in TP was statistically significant after 30 minutes of gargling. Gargling with different concentrations of NaCl solutions resulted in significant reductions in TP in all the groups. There was a significant decrease in TP in the group preloaded with 1000 ml of distilled water at 5 minutes of rehydration. At 20 minutes TP was abolished suggesting that approximately 1000 ml of water was needed for the rehydration. These results show that baseline TP in euhydrates is elevated and that TP increases in dehydrated subjects. Gargling reduces TP, but did not abolish thirst. It is suggested that a fall in plasma osmolality due to drinking may be responsible for abolishing thirst.

Using saline solutions for ACE washouts

We had found that twice-normal saline (2NS) antegrade continence enema (ACE) lavages were better than with normal saline (NS) but caused unpleasant symptoms. We therefore undertook a double-blind crossover study...

Plasma Concentrations of Arginine Vasotocin and Urotensin II Are Reduced Following Transfer of the Euryhaline Flounder (Platichthys flesus) from Seawater to Fresh Water

Plasma concentrations and stored levels of the neuroendocrine peptides arginine vasotocin (AVT) and urotensin II (UII) were measured in the euryhaline flounder (Platichthys flesus) following the acute hypo-osmotic challenge of direct seawater (SW) to fresh water (FW) transfer. Hormone measures, plasma osmolality, and ion concentrations and tissue water content were determined 1, 4, 8, 24, 72, and 144 h after transfer. Plasma AVT concentration fell initially following FW transfer but then returned toward pretransfer levels by day 6. Plasma UII concentration decreased while urophysial UII content was increased following hypo-osmotic challenge relative to SW time-matched controls, suggesting down regulation of the UII system during the initial stages after FW transfer. These changes in neuroendocrine activity were associated with a significant fall in plasma osmolality and major plasma ions. Positive correlations were observed between plasma AVT and osmolality and Cl− and Mg2+ concentrations, suggesting functional association of these plasma parameters with AVT action and/or control of AVT secretion. The initial response to hypotonic challenge involves reduced plasma AVT and UII levels consistent with the proposed role for these hormones, supporting flounder osmoregulation in hypertonic media.

The role of relaxin in the pregnancy associated reduction in plasma osmolality

Recent data suggest that the ovarian peptide relaxin is responsible for the pregnancy-associated fall in plasma osmolality in the rat. In order to test whether relaxin has the same role during human pregnancy, plasma osmolality, electrolytes, urea and creatinine were measured in samples obtained at 10, 20 and 30 weeks gestation from singleton pregnancies conceived following ovum donation (OD, n = 12), spontaneously (N, n = 12) and following in-vitro fertilization and embryo transfer (IVF, n = 14). These groups were chosen, as relaxin concentrations throughout pregnancy are undetectable (OD), elevated (IVF) or normal (N). Thus, if relaxin alone is responsible for the fall in plasma osmolality associated with pregnancy in the human, then plasma osmolality would be expected not to fall during pregnancy in the OD group and to show a consistent decline from OD to N to IVF throughout pregnancy. Plasma osmolality fell significantly during pregnancy in both the OD and N groups, but not the IVF group. In addition, plasma osmolality was only significantly greater in OD when compared with IVF group at 10 weeks gestation; thereafter there were no significant differences between the groups with regard to plasma osmolality. Similarly, at 10 weeks the plasma concentrations of sodium and potassium were significantly higher in the OD than in either the N or IVF groups. Thus, although relaxin may be important in the initial control of plasma osmolality, other factors, probably derived from or regulated by the feto-placental unit, supersede it as pregnancy advances.

Ascorbic acid concentration in the lateral hypothalamus is related to plasma osmolality

Microdialysis was used to measure extracellular ascorbic and uric acid concentrations in the lateral hypothalamus of water-restricted rats as they drank distilled water or 1.5% NaCl. Other water-restricted rats, not implanted with microdialysis probes, were decapitated 2 h after beginning to drink these fluids. Rats were inverted and their blood was collected for measurements of plasma osmolality and percent hematocrit. Results showed that drinking distilled water produced a significant increase in the ascorbic acid concentration but not in the uric acid concentration. Drinking 1.5% NaCl produced a significant decrease in the uric acid concentration but not in the ascorbic acid concentration. Drinking distilled water decreased mean osmolality from 306.0 to 291.5 mOsm/kg, whereas drinking 1.5% NaCl maintained mean osmolality at water-restricted levels. These results indicate that the extracellular fluid concentration of ascorbic acid in the lateral hypothalamus rises in response to a fall in plasma osmolality.

The role of the pineal in the control of the daily patterns of neurohypophysial hormone secretion.

Plasma concentrations of neurohypophysial hormones show clear rhythms over 24 hr which can be suppressed by exposure to constant light, an observation consistent with pineal involvement. A study has therefore been performed on the changes in the hormone levels in the hypothalamus, posterior pituitary, and plasma over 24 hr in control, pinealectomised, and sham pinealectomised animals to determine if the pineal could play a role. Water intake, urine excretion, packed cell volume, plasma osmolality, and electrolytes were also monitored. Pinealectomy had little effect on fluid balance, but after 8 weeks for oxytocin and 2 weeks for vasopressin the morning values (0700-0800) for the circulating concentrations of the hormones were significantly higher in the pinealectomized group compared with the combined sham operated and unoperated groups (pineal intact). By contrast, the pituitary vasopressin was significantly lower in the pinealectomised group. The increase in plasma oxytocin and vasopressin seen over the hours of daylight and accompanying fall in plasma osmolality seen in the pineal intact group were absent in the pinealectomised group. Similarly, the evening fall in pituitary hormone concentrations and increase in hypothalamic hormone content were absent in the pinealectomised animals. After 10 days of exposure to constant light, the fall in plasma osmolality in the pineal-intact animals over the day was no longer significant; instead a significant increase in plasma osmolality and sodium was seen in the pinealectomised group. Exposure to constant light, while altering the patterns of neurohypophysial activity in the pineal intact group, had little effect on the pinealectomised animals.

Erythrocyte hydration in normal human pregnancy

OBJECTIVE To determine whether the fall in plasma osmolality in normal human pregnancy resulted in cellular overhydration. DESIGN The changes in erythrocyte hydration, potassium and total osmoles in response to a decrease in osmolality in vitro and associated with the fall in plasma osmolality in normal pregnancy were determined. SUBJECTS Fifty-one women were studied serially during pregnancy and again 20 weeks after delivery. RESULTS Erythrocytes from pregnant women exposed in vitro to a 29.9% osmolality decrement had a 28.5% increase in cell hydration. At 14 weeks gestation although plasma osmolality was lower than after delivery (281.1 vs 291.6 mosmol/kg; P less than 0.001) both erythrocyte hydration (1.83 l/kg dry weight cells) and potassium (264 mmol/kg) contents were reduced from the nonpregnant values (1.88 l/kg; P less than 0.01; 272 mmol/kg; P less than 0.001). For the remainder of pregnancy plasma osmolality remained at this lower level but cell hydration and potassium both increased to values at 38 weeks gestation that were greater than in the nonpregnant state (1.92 vs 1.88 l/kg; 287 vs 272 mmol/kg). CONCLUSIONS These findings suggest that a loss of cell osmoles may be a primary event affecting cell hydration in pregnancy and plasma osmolality is then reduced to maintain normal cell hydration. Subsequent changes in cell hydration were led by changes in intracellular osmole content.

Erythrocyte hydration in normal human pregnancy

To determine whether the fall in plasma osmolality in normal human pregnancy resulted in cellular overhydration. The changes in erythrocyte hydration, potassium and total osmoles in response to a decrease in osmolality in vitro and associated with the fall in plasma osmolality in normal pregnancy were determined. Fifty-one women were studied serially during pregnancy and again 20 weeks after delivery. Erythrocytes from pregnant women exposed in vitro to a 29.9% osmolality decrement had a 28.5% increase in cell hydration. At 14 weeks gestation although plasma osmolality was lower than after delivery (281.1 vs 291.6 mosmol/kg; P less than 0.001) both erythrocyte hydration (1.83 l/kg dry weight cells) and potassium (264 mmol/kg) contents were reduced from the nonpregnant values (1.88 l/kg; P less than 0.01; 272 mmol/kg; P less than 0.001). For the remainder of pregnancy plasma osmolality remained at this lower level but cell hydration and potassium both increased to values at 38 weeks gestation that were greater than in the nonpregnant state (1.92 vs 1.88 l/kg; 287 vs 272 mmol/kg). These findings suggest that a loss of cell osmoles may be a primary event affecting cell hydration in pregnancy and plasma osmolality is then reduced to maintain normal cell hydration. Subsequent changes in cell hydration were led by changes in intracellular osmole content.

Effect of ovariectomy and treatment with ovarian steroids on vasopressin release and fluid balance in the rat

Plasma vasopressin concentrations have previously been shown to vary during the oestrous cycle of the rat, being highest on the morning of pro-oestrus and lowest on dioestrus day 1. To determine the effect of gonadal steroids on vasopressin secretion and fluid balance, mature rats were ovariectomized and given oestrogen, progesterone or vehicle alone s.c. for periods of up to 16 days. Plasma vasopressin concentrations fell after ovariectomy and this was reflected in an increase in 24-h urine volume. The normal increase in plasma vasopressin concentrations seen over day-light hours was also suppressed. The change in vasopressin concentrations observed on steroid treatment depended upon both the dose and the duration. High doses of oestrogen were associated with a fall in plasma vasopressin, probably as a result of fluid retention. Thus, of an initial group of rats given silicone elastomer implants containing 50, 500 or 1000 micrograms oestradiol in oil, plasma vasopressin concentrations were reduced after 7 days treatment with 1000 micrograms oestradiol implants in association with reduced plasma sodium concentrations. Daily s.c. injections of 100 micrograms oestradiol benzoate/100 g body weight produced an immediate small increase in plasma vasopressin concentrations, but by 14 days the plasma concentrations of 0.7 +/- 0.16 pmol/l (mean +/- S.E.M.) had fallen significantly and were less than those in the vehicle-treated group (1.2 +/- 0.26 pmol/l). However, after treatment for 14 days with implants containing only 50 micrograms oestradiol, plasma vasopressin concentrations were higher compared with the group receiving vehicle alone, despite the fact that the plasma osmolality was lower in the latter group, suggesting a long term resetting of the osmoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma osmolality predicts extracellular fluid catechol concentrations in the lateral hypothalamus.

The lateral hypothalamus has an important role in regulating food and water intake. We have investigated the endogenous release of monoamines from the lateral hypothalamus during manipulations of plasma osmolality and circulating volume. Adult male Sprague-Dawley rats implanted with carbon paste in vivo electrochemical (EC) electrodes in the lateral hypothalamus were placed on a 72-h water deprivation schedule. Although the carbon paste EC electrode has an intrinsically ambiguous signal in which changes in ascorbic acid may appear as changes in catechol concentrations, pharmacologic studies in lateral hypothalamus indicated that the electrode most likely measured norepinephrine and possibly epinephrine. On the test day, the EC electrodes were scanned with linear sweep voltammetry from -0.2 to +0.4 V at a rate of 5 mV/s. Semiderivative signal processing showed catechol and hydroxyindole peaks at +0.11 and +0.23 V, respectively. Baseline recordings were made prior to rats drinking distilled water, 10% sucrose, 5% dextrose, 0.30% NaCl, 0.90% NaCl, or 10% d-mannitol. To control for the act of drinking, other implanted dehydrated rats were intraperitoneally injected with 5% dextrose, 0.30% NaCl, or 0.90% NaCl. To dissociate the effects of osmolality and circulating volume on the EC response, hydrated rats implanted with EC electrodes were subcutaneously injected with 12% NaCl or intraperitoneally injected with 35% polyethylene glycol. Other rats subjected to water deprivation and osmotic challenges were decapitated and trunk blood was collected for measurements of plasma osmolality and hematocrit. Similar experiments were conducted using homozygous Brattleboro rats which lack arginine vasopressin (AVP) but which preserve normal plasma osmolality with prodigious drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Osmoregulation and control of vasopressin secretion in healthy humans.

The functional characteristics of osmoregulated vasopressin secretion can be defined in terms of an osmotic threshold for its release and a sensitivity of the osmoreceptor and vasopressin-secreting unit. Osmotically stimulated thirst has features similar to osmoregulated vasopressin. There are wide individual variations in the functional characteristics of both thirst and vasopressin release in healthy humans, probably genetic in origin. The influence of aging appears to enhance the sensitivity of vasopressin secretion but blunt thirst appreciation. Yet in many physiological situations changes in osmoregulated vasopressin release and thirst occur in parallel. The fall in plasma osmolality associated with human pregnancy is accounted for entirely by a lowering of the osmotic thresholds for thirst and vasopressin release. Similar but less marked alterations accompany the ovulatory luteal phase of the menstrual cycle. A major nonosmotic stimulus to vasopressin secretion is hypotension and/or hypovolemia, mediated by high- (carotid sinus) and low- (left atrial) pressure receptors. Circulating catecholamines influence the release of vasopressin by alpha- and beta-adrenergic pathways. Drinking by hypertonic humans provides immediate reduction in thirst and vasopressin secretion probably mediated by pathways from the oropharynx. The modest but variable rise in plasma vasopressin in response to hypoglycemia appears to be due to cellular neuroglycopenia and is independent of parasympathetic pathways. Although osmotic and hemodynamic stimuli to vasopressin release do not act independently of each other, the precise subtle interactions between them and other nonosmotic stimuli remain to be clarified.

Increased PGE2 excretion by dDAVP in humans depends on state of hydration.

The relationship of renal prostaglandin E2 (PGE2) excretion (UPGEV) to water deprivation, water diuresis, and subsequent antidiuresis by 1-desamino-8-D-arginine vasopressin (dDAVP) was studied in female volunteers. After 16 h of water deprivation, the subjects began a sustained water diuresis for 8 h. This diuresis caused a transient twofold rise in UPGEV at 2 h (P less than 0.05), which then fell back to or below baseline levels. dDAVP given during the water diuresis caused a transient rise of UPGEV as urine volume decreased and plasma osmolality fell from 277 +/- 1.5 to 271 +/- 2 mosmol/kg (P less than 0.01). Another group of subjects had the water diuresis discontinued after 4 h with dDAVP given at the 5th h when urine volume was decreasing and urine osmolality was increasing. In this setting dDAVP did not produce as great a fall in plasma osmolality nor did it increase UPGEV. These data indicate that renal prostaglandin synthesis (as determined by UPGEV) is increased transiently by an acute water load; dDAVP given during continued water ingestion results in a fall in plasma osmolality and increased PGE excretion; however, dDAVP does not increase UPGEV during normal hydration; and UPGEV is independent of changes in urine flow. These findings imply that renal prostaglandins may have a functional role in humans to inhibit the hydroosmotic actions of antidiuretic hormone, and thus hasten the excretion of a water load, and to prevent overhydration when inappropriate antidiuresis occurs. However, there is no evidence that the stimulus for prostaglandin production is dDAVP per se.

Development of a cytochemical assay for plasma vasopressin: application to studies on water loading normal man.

A cytochemical assay has been developed to measure human plasma arginine vasopressin. It is based on the stimulation of Na+-K+, ATPase activity located in the outer medulla of the rat kidney, and is capable of detecting very low plasma arginine vasopressin concentrations, limit of detection 0.01 pmol/l. Specificity for vasopressin stimulation of the enzyme is conferred on the assay by the use of specific vasopressin antiserum. Index of precision of the assay is 0.21. Degradation of arginine vasopressin in plasma in inhibited by phenanthroline. Samples may be stored up to 8 weeks at -70 degrees C. Intra- and inter-assay coefficients of variation were 22% (n = 8) and 104% (n = 12), respectively. A sustained water load in eight healthy male adults caused a fall in plasma osmolality from a basal of 286.5 +/- 2.0 (mean +/- SEM) to 279.2 +/- 2.4 mmol/kg after the load (P less than 0.001), which was associated with a reduction in urine osmolality from 867 +/- 54 to 69 +/- 3 mmol/kg. Plasma immunoreactive arginine vasopressin fell from 1.3 +/- 0.3 pmol/l to become undetectable (less than 0.3 pmol/l), but plasma cytochemical arginine vasopressin decreased from 0.96 +/- 0.14 to 0.07 +/- 0.02 pmol/l. There was a curvilinear relationship between plasma osmolality and plasma cytochemical arginine vasopressin, which militated against the concept of an osmotic threshold for vasopressin release.

The effect of acutely reduced plasma osmolality on acute renal failure in rats.

The present study was designed to evaluate the effect of acute fall in plasma osmolality in three models of acute tubular necrosis in rats: (a) glycerol, (b) arterial clamping and (c) mercuric chloride. Plasma osmolality was reduced by a water loading during a mild anaesthesia from 305 +/- 7 to 270 +/- 12 mosmol/kg of water (P less than 0.01). In the ischaemic models of acute tubular necrosis (glycerol and arterial clamping), during the first 24 h in rats with reduced plasma osmolality, the respective creatinine clearance rates (CCR), 0.04 +/- 0.02 and 0.06 +/- 0.04 ml/min, were strikingly lower than those in rats with normal osmolality, 0.21 +/- 0.03 and 0.26 +/- 0.06 ml/min (P less than 0.001) respectively. The control CCR were 0.65 +/- 0.07 and 0.62 +/- 0.07 ml/min respectively. During the second day after induction of ischaemic (glycerol and arterial clamping) acute tubular necrosis, rats with reduced plasma osmolality exhibited a similar worsening in CCR as on the first day, when compared with that in rats with normal osmolality. In rats with acute tubular necrosis induced with mercuric chloride reduction in plasma osmolality did not aggravate the severity of renal failure. These results show that acute fall in plasma osmolality worsens the renal failure in the ischaemic but not in the nephrotoxic models of acute tubular necrosis.

Role of antidiuretic hormone in impaired water excretion of patients with congestive heart failure.

Plasma antidiuretic hormone (ADH), PRA, plasma osmolality, and the parameters of renal water excretion were measured after overnight dehydration and for 5 h after an oral load in 14 patients with congestive heart failure (CHF) treated with diuretics (group 1), 8 hypertensive patients without CHF also treated with diuretics (group 2), and 11 patients with coronary artery disease but without CHF who were not treated with diuretics (group 3). Under basal conditions, mean plasma osmolality was lower in group 1 than in group 3, but was not different in groups 1 and 2. Mean plasma ADH was higher in group 1 than in group 2 or 3. In response to the water load, plasma osmolality and plasma ADH levels decreased in the 3 groups. ADH levels remained significantly greater in group 1 than in groups 2 and 3 from 2-4 h after the water load despite more marked hypoosmolality in group 1 compared with that in either of the 2 control groups. Plasma ADH was significantly correlated with plasma osmolality only in the 2 control groups. Mean PRA was greater in patients with CHF and patients without CHF treated with diuretics than in untreated patients. Cumulative water excretion was lower in patients with CHF than in patients in the 2 control groups from 2-5 h after the water load. At 5 h, the mean percentage excretion of the ingested loads was 56.8%, 90.7%, and 91.2% in the patients of groups 1, 2, and 3 respectively. Free water clearance was lower and minimal urinary osmolality was greater in the patients with CHF than in those in the 2 control groups. Two patients with CHF, who excreted more than 75% of the water load, also had low plasma basal ADH levels. These data show that patients with CHF have an inappropriate response of plasma ADH to a marked fall in plasma osmolality. This disorder is not due to the diuretic therapy, since hypertensive patients treated with diuretics behaved similarly to untreated patients without CHF. The reasons for this inappropriate response of plasma ADH during a water load in patients with CHF are probably multifactorial.

The effects of postural changes on ADH release and the renal handling of sodium and water in patient with idiopathic edema.

In order to investigate the role of ADH and the renal handling of sodium and water in patients with idiopathic edema, 21 patients were subjected to acute oral water load tests. Although a normal water diuresis was observed in al patients in supine posture, it was markedly impaired in upright posture with significant decreases in sodium, free water, and osmolar clearances. In particular, two patients exhibited the continuous production of concentrated urine after the water load in upright posture. The fractional reabsorption of sodium at the proximal tubules was significantly increased in upright posture, while the glomerular filtration rate did not change significantly. The constricting of both legs with elastic bandages tended to improve the water diuresis in upright posture, suggesting that the pooling of blood into the lower legs might be contributing to the formation of idiopathic edema. The patients showed normal osmoregulation of ADH release in supine, but not in upright posture: the suppression of ADH release in upright posture was only transient or incomplete despite a sufficient fall in plasma osmolality following the water load. Thus, both an increase in renal sodium reabsorption and the insufficient suppression of ADH release in upright posture might contribute to the retention of body fluid in patients with idiopathic edema.

Inappropriate drinking and secretion of vasopressin after caval constriction in dogs.

The object of this study was to determine if chronic thoracic vena caval constriction affected mechanisms regulating water balance, independent of known changes in sodium metabolism in the dog. Fluid and electrolyte balances were determined for 5 days before and 14 days after constriction of the vena cava (n = 5) and in a separate population of time controls (n = 4). Cardiac output was reduced and heart rate was increased in response to chronic caval constriction although blood pressure was maintained at control levels. Water intake and plasma arginine vasopressin (AVP) increased from 31 +/- 4 ml/kg and 1.3 +/- 0.2 pg/ml during the control period to 81 +/- 6 ml/kg and 3.4 +/- 0.6 pg/ml during the period of caval constriction. The caval dogs developed a positive water balance, which preceded the development of a positive sodium balance. This led to a significant fall in plasma osmolality from a control mean of 296 +/- 1 to 284 +/- 4 mosmol/kg during caval constriction and dilutional hyponatremia. Plasma and blood volume increased significantly in response to constriction and were accompanied by formation of 123 +/- 10 ml/kg of ascitic fluid. These results show that water intake and plasma levels of AVP were increased in spite of a fall in plasma osmolality and an increase in vascular volume. These responses cannot be secondary to sodium retention because water was retained in excess of sodium hence hyponatremia. Therefore, chronic caval constriction causes a profound primary disturbance in mechanisms regulating water balance, which may contribute to the formation of edema fluid.