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.     

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.     

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.     

Time course of changes in renal tissue and urinary composition after cessation of constant infusion of lysine vasopressin in the conscious, hydrated rat

1. The changes in urinary and renal tissue composition in conscious rats were determined for up to 2 hr following the cessation of intravenous infusion of lysine vasopressin, LVP (at 60 muu./min. 100 g body wt. for 4(1/2) hr). A constant water load (4% body wt.) was maintained during and after lysine vasopressin infusion, by quantitative replacement of excreted water. In these circumstances, any changes in urinary and renal tissue composition are presumed to represent direct consequences of the rapid plasma and tissue clearance of lysine vasopressin.2. Urinary flow increased and osmolality decreased, rapidly, reaching stable values characteristic of sustained water diuresis after about 60 min.3. The steepness of the corticomedullary solute concentration gradients also decreased rapidly. Papillary Na and urea concentrations fell to values characteristic of sustained water diuresis in about 45 min.4. The changes in medullary composition were compounded of a moderate significant increase in water content, a moderate, significant decrease in Na content, and a profound decrease in urea content.5. In the eventual steady-state water diuresis, urinary outputs of Na and K were significantly lower, and of NH(4) significantly higher, than those observed in control experiments where LVP infusion was continued for the corresponding 2 hr.6. It is concluded that the diuresis following the cessation of LVP infusion is due not merely to reduced nephron permeability to water but also to a rapid reduction in the osmotic force responsible for water reabsorption from the collecting duct.     

Effects of intraruminal loads of saline or water followed by voluntary drinking in the dehydrated lactating goat

In five goats water deprivation for 26 h increased plasma osmolality, total plasma protein concentration, and plasma vasopressin (AVP) concentration to higher levels during lactation compared to nonlactation. At the end of the dehydration period intraruminal loads of saline or water (corresponding to 50% of the body weight loss) were given to lactating goats. The saline load decreased the plasma protein concentration below control levels, while plasma osmolality, Na concentration and AVP did not change. After the water load the plasma protein concentration stayed elevated. Plasma osmolality, Na concentration and AVP fell, but remained significantly above control levels. Both plasma renin activity (PRA) and aldosterone (PA) concentration increased after water, but decreased after saline administration. Three hours after the fluid loads the goats were offered water to drink. AVP decreased at the sight of water. After drinking, plasma osmolality, Na and AVP continued to decrease in water loaded animals, and fell also in saline loaded goats. PRA remained elevated, and PA increased in water loaded goats, while these hormones still were depressed in saline loaded goats. Mean renal 'free water clearance' became positive after drinking in both groups. It is concluded that the water losses with the milk cause lactating goats to become dehydrated more rapidly than non-lactating goats during water deprivation. Lowering of the plasma osmolality and Na concentration are more important than restoration of the plasma volume in suppressing the high plasma AVP concentration in the dehydrated lactating goat. The water diuresis, which occurred after voluntary drinking, indicates that the goats had not been able to anticipate their water deficit accurately.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

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.     

Vasopressin release in response to intracerebroventricular L-alanine and L-arginine, and its dependence upon CSF NaCl concentration

Influences on renal water, electrolyte, and arginine vasopressin (AVP) excretions of 1 h infusions (20 microliters/min) of a neutral (L-alanine) and two basic (L-lysine and L-arginine) amino acids into the lateral cerebral ventricle were studied in hydrated goats, and were compared to effects of control infusions of hypertonic (0.25 M) NaCl. L-alanine (0.11 M) dissolved in hypotonic NaCl caused more pronounced inhibition of the water diuresis and greater increase in AVP excretion than did the control infusions, but, in comparison to the latter, the responses developed very slowly. The effects were further delayed and were much attenuated when L-alanine was administered in isotonic glucose, but became considerably accentuated when isotonic NaCl was used as the solvent. L-lysine (0.09 M) in hypotonic NaCl did not inhibit the water diuresis or cause any apparent AVP release, whereas the corresponding L-arginine infusions caused inhibition of the water diuresis and increase in AVP excretion of approximately the same magnitudes and time courses as the control infusions. Like for L-alanine, these effects became accentuated when L-arginine was dissolved in isotonic NaCl, and became delayed and much attenuated when isotonic glucose was used as the solvent. L-arginine induced a more pronounced increase in renal Na excretion than did L-alanine and 0.25 M NaCl. Since transport together with Na (increasing the Na influx) generally is much more important for cellular uptake of neutral than of basic amino acids, the possibility is discussed that L-alanine here might have caused AVP release by increasing transmembrane Na transport of juxtacerebroventricular Na sensors regulating the AVP secretion--a suggestion supported by the lack of response to the basic L-lysine. The antidiuretic effect of the other basic amino acid, L-arginine, can not be explained along this line. However, with regard to the characteristic differences observed between the responses to L-alanine and L-arginine, the possibility is discussed that the latter might not have acted at a sensory level, but on the final neuronal link in the release of neurohypophyseal hormones, the hypothalamic neurosecretory cells. In contrast to L-alanine and L-arginine, L-lysine appeared to stimulate the appetite of the goats.     

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)     

Deuterium Induced Extinction of ADH-release in Response to Intracerebroventricular Infusions of Hypertonic NaCl and Angiotensin

Infusions (20μl/min) of hypertonic (0.3 M) NaCl and angiotensin 11 (1 ng/kg min^-1)in isotonic (0.15 M) NaCl were made for 1 h in the hydrated goat during fully developed water diuresis. Either H₂O or deuterium (D₂O) was used as solvent. A pronounced antidiuretic response, outlasting the infusion period by 30 min or more, was seen when the substances were dissolved in H₂O. Only a weak inhibition of the water diuresis, which was extinguished during the infusion period, was obtained when D₂O was used as the solvent. The infusion of 0.3 M NaCl/H₂O invariably induced drinking in one of the goats, which, however, showed no drinking response to the infusions of 0.3 M NaCl/D₂O. The possibility is discussed that D₂O (perhaps by-its inhibitory effect on (Na+-K+)-ATPase activity) reduced the sensitivity of juxtaventricular receptors regulating ADH-release and water intake.     

Insulin secretion induced by glucose and by stimulation of β2-adrenoceptors in the rat. Different sensitivity to somatostatin

The effects of somatostatin on insulin secretion stimulated by glucose or by the selective β₂-adrenoceptor agonist terbutaline were studied in vivo in the anaesthetized rat. Infusion of low doses of glucose (5mg/min) or terbutaline (2 μg/min) caused slight stimulation of insulin secretion, whereas infusion of higher doses of glucose (12.5mg/min) or terbutaline (200 μg/min) yielded higher rates of insulin release. In both instances plasma insulin concentrations were of comparable magnitudes immediately prior to somatostatin infusion. Somatostatin (0.1 μg/min) inhibited the insulin response to glucose and terbutaline, both at the low and high secretory rates. However, the inhibitory effect of somatostatin was much more pronounced on insulin release during glucose infusion than during infusion of terbutaline. Thus, at the high rate of insulin secretion somatostatin depressed plasma insulin by 46% during glucose and by 22% during terbutaline infusion. The results at the low rate of insulin secretion were 66% and 48%, respectively. Both at high and low secretory rates somatostatin depressed plasma insulin levels more potently during glucose infusion than during terbutaline infusion (P < 0.001 and P < 0.05, respectively). Furthermore, the plasma insulin levels during inhibition by somatostatin following terbutaline stimulation stabilized after approximately 10min of somatostatin infusion, whereas following glucose stimulation the insulin levels continued to decline. The results suggest that somatostatin inhibits insulin secretion via mechanisms that are more closely related to the insulin secretory pathway induced by glucose than to that induced by β-adrenoceptor agonists.     

Biphasic change in plasma potassium concentration by mannitol infusion in rats.

Changes in plasma Na+([Na+]pl) and K+([K+]pl) concentrations were continuously measured in nephrectomized rats consequent to intravenous infusion of isosmotic mannitol (M group) or sucrose (S group) at 1.6 ml/100 g body wt. for 10 min, and for the following 30 min. The effect of a Ca2+ channel blocker (diltiazem, 0.1 mg/100 g body wt.) was also evaluated. In the S group, [K+]pl decreased during the infusion and rose above the control level after the discontinuance of infusion. In the M group, [K+]pl gradually increased even during the infusion and reached the same level as the S group at the end of the experiment. In both the S and M groups, [Na+]pl decreased, while PaCO2, pH, and HCO3- did not change. The increase in [K+]pl in the M group had two components. The first was a transient component as presented by the difference of [K+]pl between the M and S group. It might be attributable to K+ release from the intracellular space during a regulatory volume decrease consequent to cell swelling induced by isosmotic mannitol infusion. The second component of the increase in [K+]pl after the infusion was observed in both groups, and this increase might be related to the dilution of ions induced by the large amount of infused nonelectrolyte solution. Diltiazem suppressed both of these changes in [K+]pl, suggesting that they are related to Ca2+ channels. The results suggest that increase in [K]pl by isosmotic mannitol infusion is related to the effects of regulatory volume decrease and dilutional effect.     

Comparison of passive heat or exercise-induced dehydration on renal water and electrolyte excretion: the hormonal involvement

The effects of hydromineral hormones and catecholamines on renal water and electrolyte excretion were examined during and after dehydration induced by either passive heat or exercise. Eight healthy young Caucasian subjects participated in three separate trials, each including three consecutive phases. Phases 1 and 3 involved a 90-min period at rest in a thermoneutral environment, while phase 2 involved a 120-min period designed to provide: (1) euhydration (control trial), (2) passive heat-induced dehydration of 2.8% body mass, or (3) exercise-induced dehydration of 2.8% body mass. During the two dehydration procedures, the decreases in urine flow and sodium excretion were more marked during exercise (P<0.05). An increase in plasma catecholamines occurred only during exercise, together with a reduction in creatinine clearance and more marked increases in plasma renin and aldosterone than during passive heat exposure (P<0.05). Although plasma vasopressin was elevated during the two dehydration procedures, urine osmolality did not change and, moreover, free water clearance increased during exercise (P<0.05). Plasma levels of atrial natriuretic peptide increased markedly only during exercise compared to the other trials (P<0.05). After the dehydration procedures, urine flow decreased again and urine osmolality increased markedly (P<0.05), while plasma vasopressin remained elevated. These results suggest that sympatho-adrenal activation during exercise plays a major role in the more marked reduction in diuresis and natriuresis than during passive heat exposure. Despite high plasma vasopressin concentrations during the two dehydrating events, the observed antidiuresis was not due to an increased renal concentrating ability, and the vasopressin was more effective after the dehydration procedures. Electronic Publication     

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.     

Effects of fluid intake on basal and vasopressin-responsive urinary prostaglandin E

The effects of fluid intake on basal and vasopressin-responsive urinary PGE excretion (UPGEV) were examined in conscious rats under conditions of 1) ad libitum water intake, 2) water deprivation, and 3) water diuresis induced by ad libitum intake of 5% dextrose in water. UPGEV fell progressively during 40 h of water deprivation. Water diuresis after water deprivation increased UPGEV transiently (8 h). Vasopressin (Pitressin tannate in oil, 5 U/kg subcutaneously) increased UPGEV and decreased urine volume (V) in rats on ad libitum water intake but did not alter UPGEV during water deprivation. Indomethacin suppressed UPGEV (70-90%), increased basal urine osmolality (Uosmol), and potentiated the antidiuretic response to Pitressin in rats on ad libitum water intake. Indomethacin accelerated by 8 h the onset of maximal antidiuresis in water-deprived rats but did not significantly alter water balance. During water diuresis, UPGEV declined in the first 8 h after Pitressin. Thereafter, UPGEV increased markedly, concurrent with early vasopressin escape. Indomethacin or meclofenamate inhibited the rise in UPGEV, the decline in Uosmol, and the increase in V of the escape phase. Indomethacin or meclofenamate also impaired the excretion of an acute water load (5% body wt) given during escape. The spontaneous decline in UPGEV during hydropenia may serve to maximize physiologic antidiuresis. Conversely, the marked increase in UPGEV induced by administration of vasopressin during water diuresis may serve to suppress the antidiuretic response and thus play a role in the mediation of escape from physiologically inappropriate antidiuresis.     

Aggravation of subclinical diabetes insipidus during pregnancy

BACKGROUND. Transient polyuria and polydipsia during pregnancy are rare, and their cause is not entirely clear. Possible explanations include the exacerbation of preexisting abnormalities in the secretion or action of vasopressin and abnormally large increases in plasma vasopressinase activity. METHODS. We studied two women in whom overt polyuria and polydipsia developed during the third trimester of pregnancy and disappeared after delivery. The secretion and action of vasopressin were studied both when the women had polyuria and polydipsia and later, when their water intake and urine volume were normal. RESULTS. One patient had partial nephrogenic diabetes insipidus. She had little increase in urine osmolality in response to water deprivation, hypertonic-saline infusion, and vasopressin injection and no response to desmopressin acetate (1-deamino-8-D-arginine vasopressin) during the immediate postpartum period. Her basal and stimulated plasma vasopressin concentrations were high (16.5 to 203.4 pmol per liter) before and during hypertonic-saline infusion 30 months post partum. The other patient had partial neurogenic diabetes insipidus. She had subnormal basal plasma vasopressin concentrations, a subnormal increase in the plasma vasopressin level and a subnormal decrease in urine flow in response to the administration of vasopressin, and a normal response to desmopressin. After pregnancy, when her urine volume was normal, she had no increase in plasma vasopressin in response to hypertonic-saline infusion, but she had a normal rise in the plasma vasopressin level and a normal renal response to vasopressin administration. CONCLUSIONS. Pregnancy may unmask subclinical forms of both nephrogenic and neurogenic diabetes insipidus. This exacerbation may result from both increased vasopressinase activity and diminished renal responsiveness to vasopressin.     

Effects of hay-feeding on acid/base balance,renal sodium excretion,aldosterone and vasopressin secretion in the goat

Effects of 30 min intense hay-feeding on acid/base and sodium homeostasis were studied in semi-starved goats during hyper- and euhydration. Parallel analyses of carotid and jugular blood samples revealed that feeding induced metabolic acidosis, which to some extent was subjected to respiratory compensation. The acidosis was accompanied by renal sodium retention and urinary acidification persisting for 2–3 h. The sodium retention was succeeded by an increase in renal Na excretion above the initial level. This natriuresis was most accentuated during hyperhydration. Blood samples taken for hormone assays during euhydration revealed a 15% increase in haematocrit and a significant rise in plasma aldosterone at termination of feeding. Inhibition of the water diuresis in hyperhydrated animals, and moderate increases in renal arginine vasopressin (AVP) excretion and plasma AVP were inconsistent effects of feeding. It is concluded, that simply jugular vein blood provides reliable information on the acid/base status of goats, but that the feeding schedule has to be considered in all experiments where small ruminants are used to investigate the integrated control of acid/base and sodium homeostasis.     

Effect of dehydration on gastrointestinal function at rest and during exercise in humans

Dehydration leads to the aggravation of gastrointestinal (GI) complaints during exercise. The aim of this study was to examine the effect of dehydration on various GI parameters during strenuous exercise. Ten healthy well-trained men were investigated in dehydrated and in euhydrated conditions. Dehydration took place before the experiments using a dehydration regimen in a sauna leading to a 3% loss of body mass. Each experiment consisted of 1 h pre-exercise rest, 1.5 h cycling at 70% maximal exercise intensity, and 3.5 h post-exercise rest. During cycling, liquid gastric emptying (GE), orocaecal transit time (OCTT) and intestinal permeability and glucose absorption were measured. The GI-symptoms were scored using a questionnaire. Body temperature, plasma volume and vasopressin were measured before and after cycling. The GE was significantly slower during dehydration [median time to peak ¹³C enrichment in the breath sample (¹³C-TTP) 23.6 min, range 13.7–50.0 min, P=0.02] than in the control situation (median ¹³C-TTP 17.1 min, range 9.8–38.4 min). The OCTT was unchanged (median 173 min, range 98–263 min compared to median 128 min, range 98–195 min, P=0.18). Dehydration did not change intestinal permeability, glucose absorption, plasma volume, rectal temperature or plasma vasopressin concentration. In the dehydration experiment, exercise induced a significant increase in nausea (P=0.01) and epigastric cramps (P=0.05), in contrast to the control situation. In both experiments, exercise led to a significant increase in rectal temperature and plasma vasopressin concentration, and a significant decrease in plasma volume. The increase in plasma vasopressin concentration was significantly higher in the dehydration experiment (P=0.015). No significant differences in either the post-exercise rectal temperatures or in plasma volumes was observed. The difference in GE between the two experiments was significantly correlated with the difference in nausea score (r=0.87, P=0.002). We concluded that dehydration leads to a delayed GE but not to differences in OCTT, intestinal permeability or glucose uptake during intense cycling. The delay in GE is significantly associated with an increase in exercise-induced nausea. Accepted: 24 July 2000     

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.