Control of water intake in thermally dehydrated rats

Male rats were thermally dehydrated by exposure without water to an environmental temperature of 40 degrees C for 0-4 hr or to environmental temperatures of 25-40 degrees C for 4 hr. Water intake was then measured for 2 hr or a blood sample was taken to determine the effect of heat exposure on body water status. Evaporative water loss and water intake increased with increased duration and severity of heat exposure. Heat exposure significantly increased plasma osmolality and plasma sodium concentration and significantly decreased plasma potassium concentration. Hematocrit and plasma protein concentration increased slightly but not significantly with heat exposure. The increases in water intake in association with increases in evaporative water loss, plasma osmolality and plasma sodium concentration with no significant increases in hematocrit or plasma protein concentration indicates that the thirst induced by thermal dehydration is primarily osmotic in nature. Water intake equal to about 50% of the evaporative plus urinary water loss reduced plasma osmolality and sodium concentration to control levels, removing the stimulus to drink before the water loss was replaced.     

Mechanism of cold diuresis in the rat

The effect of cold exposure (CE) on renal water excretion has not been clearly delineated. Conscious rats were exposed to decreased ambient temperature (15 degrees C). Forty-five minutes of CE resulted in reversible increases in urine flow and decreases in urine osmolality. The diuresis was not due to a diminished response to vasopressin (VP), as the antidiuresis associated with 500 microU of Pitressin given to water-diuresing rats was comparable at 15 and 30 degrees C. To determine whether the diuresis was due to intrarenal factors, glomerular filtration rate, renal blood flow, sodium excretion, and osmolar clearances were measured and found to be equivalent during control and cold conditions. To determine whether the observed diuresis was due to suppression of endogenous VP, VP-free Brattleboro rats undergoing a constant VP infusion were cold exposed. In these rats, CE was not associated with a change in either urine flow or urinary osmolality. This antidiuretic hormone-mediated mechanism was corroborated by a decrease in immunoassayable VP levels. To determine the mechanism whereby CE suppresses endogenous VP, plasma osmolality and hemodynamic parameters were measured. Although CE was not associated with a change in plasma osmolality, it did result in a significant increase in both mean arterial pressure and cardiac index. Pretreatment of rats with 6-hydroxydopamine prevented both the increase in mean arterial pressure and cold diuresis. We conclude that the diuresis observed upon exposure to 15 degrees C results from nonosmotic suppression of endogenous VP, as a consequence of the increase in mean arterial pressure.     

Thirst and hydration: Physiology and consequences of dysfunction

The constant supply of oxygen and nutriments to cells (especially neurons) is the role of the cardiovascular system. The constant supply of water (and sodium) for cardiovascular function is the role of thirst and sodium appetite and kidney function. This physiological regulation ensures that plasma volume and osmolality are maintained within set limits by initiating behaviour and release of hormones necessary to ingest and conserve water and sodium within the body. This regulation is separated into 2 parts; intracellular and extracellular (blood). An increased osmolality draws water from cells into the blood thus dehydrating specific brain osmoreceptors that stimulate drinking and release of anti diuretic hormone (ADH or vasopressin). ADH reduces water loss via lowered urine volume. Extracellular dehydration (hypovolaemia) stimulates specific vascular receptors that signal brain centres to initiate drinking and ADH release. Baro/volume receptors in the kidney participate in stimulating the release of the enzyme renin that starts a cascade of events to produce angiotensin II (AngII), which initiates also drinking and ADH release. This stimulates also aldosterone release which reduces kidney loss of urine sodium. Both AngII and ADH are vasoactive hormones that could work to reduce blood vessel diameter around the remaining blood. All these events work in concert so that the cardiovascular system can maintain a constant perfusion pressure, especially to the brain. Even if drinking does not take place ADH, AngII and aldosterone are still released. Furthermore, it has been observed that treatment of hypertension, obesity, diabetes and cancer can involve renin-AngII antagonists which could suggest that, in humans at least, there may be dysfunction of the thirst regulatory mechanism.     

Body fluid changes, thirst and drinking in man during free access to water

To investigate whether human thirst and drinking during ad lib access to water occur in response to body fluid deficits, we obtained blood samples and visual analog scale thirst ratings from five healthy, volunteer, young men at hourly intervals and when they were thirsty during a normal working day. Although there were significant increases in ratings of thirst, pleasantness of drinking water, mouth dryness and unpleasantness of the taste in the mouth when subjects were thirsty enough to drink compared with intervening intervals, there were no concomitant changes in body fluid variables (microhematocrit, plasma osmolality and plasma sodium, potassium, protein and angiotensin II concentrations). Subjects drank mainly in association with eating and were not overhydrated as indicated by constantly hypertonic urine and significant tubular reabsorption of free water over the experimental period. The results indicate that during free access to water humans become thirsty and drink before body fluid deficits develop, perhaps in response to subtle oropharyngeal cues, and so provide evidence for anticipatory thirst and drinking in man.     

Effect of somatostatin on kidney function and vasoactive hormone systems in healthy subjects

Summary The acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0±0.25 vs 2.4±0.2 ng AngI/ml/h;p}<0.01) and glucagon levels (40±11 vs 20±16 pg/ml;p}<0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE₂, and PGF_2alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r=0.7;p}<0.001) and urinary postaglandin E₂ and glomerular filtration (r=0.52;p}<0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.Abbreviations PAH paraaminohippuric acid - ANF atrial natriuretic factor - AVP arginine vasopressin - PRA plasma renin activity - ERPF effective renal plasma flow - GFR glomerular filtration rate - TRP tubular reabsorption of phosphate - NE norepinephrine - E epinephrine - DA dopamine - GH growth hormone     

The composition of maternal plasma and foetal urine after feeding and drinking in chronically catheterized ewes during the last two months of pregnancy

1. The fluid sacs and bladders of sixteen foetuses in fourteen ewes were catheterized between 81 and 92 days gestational age and the rumens of four ewes were also catheterized.2. Between 95 and 145 days gestational age in forty-six 24 hr experiments hourly samples of maternal plasma and foetal urine were obtained and in fifteen experiments foetal fluid samples were also taken at 4- to 6-hr intervals.3. The osmolality, pH, and concentrations of sodium, potassium, chloride, glucose, fructose and urea were measured on all samples.4. During experiment there was no significant variation in the composition of amniotic or allantoic fluid. Marked changes in osmolality occurred in maternal plasma and foetal urine when ewes drank after feeding, but not in ewes that received water intrarumenally via catheter while feeding or in fasting ewes. Post-prandial changes in maternal plasma osmolality may have altered transplacental water fluxes and as a result foetal plasma volume and osmolality.5. The results suggest that the foetus alters renal water retention by varying antidiuretic hormone (ADH) secretion in response to changes in blood volume and at later gestational ages plasma osmolality as well.6. Post-prandial changes in the [Na(+)]/[K(+)] ratio of foetal urine suggested that foetal adrenocorticotrophin (ACTH) secretion is influenced by variations in foetal blood volume and glucose concentrations.7. The post-prandial changes in foetal urine composition observed here support previous suggestions (Mellor & Slater, 1972) about the role of foetal urine in foetal fluid formation which were based on gestational changes in the composition of foetal fluids and urine sampled once daily during the post-absorptive state.     

Antagonistic effects of vasopressin and hypervolemia on osmotic reactivity of the thirst mechanism in dogs

The reactivity of the thirst mechanism to osmotic stimuli was examined in conscious dogs 1. under control conditions, 2. after raising the plasma vasopressin (PADH) level to about 30 muU/ml by intravenous infusion of the hormone, 3. after expansion of the blood volume by 15% by an intravenous infusion of dextran solution, and 4. after a simultaneous increase of PADH and blood-volume expansion. The osmotic thirst threshold was significantly lowered by the elevation of PADH and augmented by an expansion of blood volume, whereas no significant changes were observed when the increase in PADH and expansion of blood volume were applied simultaneously. The interactions between body-fluid osmolarity, blood volume, and vasopressin in regulation of water intake are discussed.     

Stimuli of thirst in donkeys (Equus asinus)

A study of the stimuli of thirst was conducted on six feral donkeys. Donkeys were found to be stimulated to drink by overnight water deprivation, by the diuretic furosemide, and by hypertonic saline infusion, all in the absence of heat stress or work. Donkeys compensate accurately for the fluid deficit caused by overnight water deprivation. After 19 hr without water, they drank 8.8 +/- 2.4 (mean +/- SE) liters within 60 min. Their undeprived overnight intake was 8.4 +/- 1.5 liters. However, latency was longer and water intake was less than that of ponies with the same changes in blood parameters, suggesting that donkeys have a higher thirst threshold than ponies. Further, plasma volume fell less in donkeys, but osmotic changes were similar to those reported in ponies exposed to the same deprivation. Donkeys infused with 250 ml of 15% NaCl drank 0.7 +/- 0.6 liters of water within 45 min, and osmolality increased from 287 to 297 mosmol/kg water; they drank no water in the same time period when infused with 250 ml 0.9% NaCl (p less than 0.05). Donkeys injected IV with 2 mg/kg furosemide drank 3.8 +/- 1.1 liters within 3 hr. Plasma protein increased from 6.9 to 7.8 g/dl. When injected with 0.9% NaCl they drank 1.0 +/- 0.5 liters (p less than 0.05). In sum, the positive thirst responses of these donkeys to cellular and extracellular dehydration were similar to those earlier demonstrated in ponies, but the results suggest a less sensitive response, albeit combined with a better internal defense of blood volume.     

Antidiuretic responses to thermal stimulation of hypothalamus and spinal cord in the conscious goat

Summary At various ambient temperatures the effects of hypothalamus temperature and spinal cord temperature on urine formation and heat production were studied in conscious goats with chronically implanted thermodes. At neutral air temperature cooling hypothalamus or spinal cord induced a fall in urine volume and a rise in urine osmolality. This antidiuretic response was concurrent with a rise in heat production. Simultaneous occurrence of antidiuresis and increased heat production was also found after cessation of hypothalamic warming. At hot ambient temperature cooling hypothalamus affected neither urine formation nor heat production. Since hypothalamic cooling and spinal cord cooling produce identical effects on kidney function it is concluded that this response is linked to the complex cold defence activity as a whole. The predominent change of free water clearance is tentatively interpreted as caused by an increased ADH concentration in the blood during the cold defence activity.     

Fluid balance and renal response following dehydrating exercise in well-trained men and women

We examined the recovery of plasma volume, plasma osmolality, renal water and sodium handling and fluid-regulating hormones to dehydrating exercise in well-trained women and compared them to men. Ten male and eight female athletes cycled at anaerobic threshold at an ambient temperature of 32°C until dehydration by 3 % of their body mass (Mb). After exercise, they drank water equal to 1 % Mb and rested for 240 min. Plasma renin activity (PRA), serum aldosterone [ALDO]_s, plasma arginine vasopressin [AVP]_pl, norepinephrine concentrations and plasma osmolality (Osm_pl) were determined at baseline, end of exercise, 30, 60, 120 and 240 min postexercise. Urine was collected at baseline, end of exercise, 60, 120 and 240 min postexercise. Renal free water and sodium handling were assessed. The recovery of OSM_pl and plasma volume occurred within the first 60 min of recovery and at similar rates between the groups. However, women had lower PRA at the end of exercise (P = 0.05), an earlier recovery of [ALDO]_s, and a slower [AVP]pl recovery. Overall fluid balance was similar between the men and women, as were the early recovery of renal free water clearance (C _{H 2}O). During the last 120 min of recovery C _{H 2}O was more negative (greater water reabsorption) and fractional sodium excretion was increased in the women compared to the men. Despite small differences in sodium and water reabsorption following dehydration, it appears from other study that recovery from dehydrating exercise in well-trained men and women is remarkably similar.     

Central osmotic regulation of sympathetic nerve activity

AIM: In this review, we will focus on the central neural mechanisms that couple osmotic perturbations to changes in sympathetic nerve discharge, and the possible impact these actions have in cardiovascular diseases such as arterial hypertension and congestive heart failure. RESULTS: Changes in extracellular fluid osmolality lead to specific regulatory responses in defence of body fluid and cardiovascular homeostasis. Systemic hyperosmolality is well known to stimulate thirst and the release of antidiuretic hormone. These responses are largely due to osmosensing neurones in the forebrain lamina terminalis and hypothalamus and are critical elements in a control system that operates to restore body fluid osmolality. An equally important, but less characterized, target of central osmoregulatory processes is the sympathetic nervous system. CONCLUSION: Understanding the neurobiology of sympathetic responses to changes in osmolality has important implications for body fluid and cardiovascular physiology. By stabilizing osmolality, vascular volume is preserved and thereby relatively normal levels of cardiac output and arterial pressure are maintained.     

Sodium and body fluid homeostasis in profiling hemodialysis treatment

Acute adverse side-effects of hemodialysis such as hypotension, muscle cramps, osmotic imbalance and thirst are induced by the interference with fluid and electrolyte balance occurring during treatment. Changes in osmolarity due to alterations of plasma sodium concentration during hemodialysis strongly influence fluid distribution between extracellular and intracellular fluid volume. Increased sodium dialysate concentration induces fluid shift from the intracellular to the extracellular compartment. This shift leads to a more efficient ultrafiltration by increasing plasma refilling volume but also to an increased thirst. Treatment of hypotension, cramps and nausea with hypertonic saline solution leads also to a considerable retention of sodium. Profiling hemodialysis consists in deliberately changing ultrafiltration and dialysate. sodium in order to combine an efficient ultrafiltration with a balanced sodium handling and to prevent side-effects during treatment. Continuous measurement and control of blood volume seems to be the best method to prevent hypotensive episodes. Profiling of sodium should not be the cause of a positive sodium balance. The clinical benefits of sodium profiling to the patients have still to be proven.     

Deviations in body fluids during fasting in rats: failure of ADH treatment and nonnutritive bulk in preventing the occurrence of plasma hypovolemia

During fasting rats initially exhibited a slight plasma hypervolemia followed by hypovolemia, with an accompanying increase in plasma osmolality, which became more severe as food deprivation continued. Urinary sodium, potassium and chloride concentrations were depressed with deprivation and this condition persisted through the six days of fasting examined. Urine osmotic pressure indicated a recovery trend by the fourth day of deprivation. This temporally coincided with a marked reduction in water consumption. In a second experiment Pitressin treatment increased urine osmolarity during four days of food deprivation, but urinary sodium and potassium concentrations were not changed nor was the plasma hypovolemia influenced. In the third experiment nonnutritive bulk in the form of Vaseline-cellulose mixture was ingested by both rats and gerbils during starvation. Water consumption and urine volume were decreased by such bulk ingestion, however, the urine remained dilute as compared with ad lib levels, and the plasma hypovolemia persisted.     

Hypodipsic hypernatremia with intact AVP response to non-osmotic stimuli induced by hypothalamic tumor: a case report

Anatomical lesions of hypothalamic area associated with hypodipsic hypernatremia have been reported only rarely. We report here a case of hypodipsic hypernatremia induced by a hypothalamic lesion. A 25-yr-old man, who had been treated with radiation for hypothalamic tumor 5-yr before, was admitted for evaluation of hypernatremia and hypokalemia. He never felt thirst despite the elevated plasma osmolality and usually refused to drink intentionally. Plasma arginine vasopressin (AVP) level was normal despite the severe hypernatremic hyperosmolar state and urine was not properly concentrated, while AVP secretion was rapidly induced by water deprivation and urine osmolality also progressively increased to the near maximum concentration range. All of these findings were consistent with an isolated defect in osmoregulation of thirst, which was considered as the cause of chronic hypernatremia in the patient without an absolute deficiency in AVP secretion. Hypokalemia could be induced by activation of the renin-angiotensin-aldosterone system as a result of volume depletion. However, inappropriately low values of plasma aldosterone levels despite high plasma renin activity could not induce symptomatic hypokalemia and metabolic alkalosis. The relatively low serum aldosterone levels compared with high plasma renin activity might result from hypernatremia. Hypernatremia and hypokalemia were gradually corrected by intentional water intake only.     

Effect of water deprivation on urinary excretion of PGE2 in the dog

We examined the influence of the state of hydration on the urinary excretion of prostaglandin E2 (PGE2) and kallikrein in the dog. Immunoreactive PGE2 and kallikrein were measured in the urine of conscious dogs during periods of water deprivation and periods of free access to drinking water and in the urine of time-control dogs that had free access to water throughout the study. During water deprivation the excretion of kallikrein did not change significantly, but PGE2 excretion increased by 50 and 75% (P less than 0.05) after 2 and 4 days, respectively, associated with reductions of body weight and urine flow and with elevation of plasma renin activity, plasma sodium, and both plasma and urine osmolality. Dehydrated dogs drank copiously when allowed free access to water, and over the following 4 days both PGE2 excretion and plasma renin activity fell significantly, associated with elevation of body weight and urine volume and with lowering of plasma sodium and plasma and urine osmolality. In contrast, if after 4 days of water deprivation the dogs were kept at a constant level of dehydration by restricting their water allotment on subsequent days to 300 ml/day, PGE2 excretion and most other variables remained at the dehydration level. In conclusion, these results suggest that renal PGE2 production is dependent on the state of hydration in the dog.     

Plasma hyperosmolality at the onset of drinking during starvation induced hypovolemia

Elevations of 2–4% in plasma osmolality were noted at the initiation of drinking following 4 days of fasting in rats. Paired animals food deprived for identical time periods but not drinking when blood sampled revealed ad lib levels of osmolality. Drinking initiation by 4 day food deprived rats following access to dry food was also accompanied by 2–4% elevations in plasma osmotic pressure. Substantial decreases in daily water consumption were observed during the 4 day food deprivation period accompanied by a mean plasma volume loss of 32% determined by T-1824 dye injection. Total blood volume loss was estimated to by 27%. Hematocrit was found to be the best estimator of plasma volume in starved rats. The elevations in plasma osmolality did not appear to be the result of uremia due to starvation induced protein catabolism. The data support the position that elevated plasma osmolality accompanies the initiation of drinking during extended fasting while return to ad lib set point osmolality accompanies cessation of drinking.     

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.     

Nonuremic hyperosmolality produced by sodium depletion

Rats were rapidly sodium depleted by a 4-hr intraperitoneal dialysis against isotonic glucose, and various serum and urine measures were taken at 4, 12 and 20 hr from the start of dialysis for dialyzed and control groups. No food or water was allowed during this postdialysis period. At 4 hr, dialyzed animals were hyponatremic, hypovolemic, hyposmolal and oliguric. This was followed by a general picture of renal sodium and chloride saving and a return of relatively normal urine volume. Plasma volume and electrolyte concentration became approximately normal as did urine glucose and urea clearances. However, serum osmolality progressively increased relative to control groups, and at 20 hr was 22.5 mOsm greater than controls. Of this difference, 15.1 mOsm was not accounted for by the osmotic equation calculated from serum sodium, glucose and blood urea nitrogen. These body water distortions in concentration and locus are discussed in the light of increased water and NaCl intakes observed in our previous research.     

Simulation study of the intercompartmental fluid shifts during hemodialysis

Hypotension is the most frequent complication during hemodialysis. An important cause of hypotension is a decrease in the intravascular volume. In addition, a decrease in plasma osmolality may be a contributing factor. Modeling of sodium and ultrafiltration (UF) may help in the understanding of underlying relationships. We therefore simulated, in a mathematical model, the intercompartmental fluid shifts during standard hemodialysis (SHD), diffusive hemodialysis (DHD), and isolated ultrafiltration (IU). We analyzed the relative theoretical effect of hydration status, dialysate sodium concentration, the initial plasma concentrations of sodium and urea, and tissue permeation to solutes on the magnitude and direction of intracellular and intravascular volume changes. This theoretical analysis shows that the transcellular fluid shifts taking place during hemodialysis treatment are, to a great part, due to inhomogeneous distribution of regional blood flow and tissue fluid volumes. During hemodialysis treatment, the cellular fluid shifts in tissue groups with relatively high perfusion and small volume occur from the intra- to the extracellular spaces. However, the fluid shift in tissue groups with a low perfusion and large volume takes place in the opposite direction. The UF volume and rates, and the size of the sodium (Na+) gradient between the dialysate and blood side of the dialyzer membrane are the most important factors influencing the fluid shifts. Higher UF volumes and flow rates cause an increasing decline in the plasma volume in both SHD and IU. High dialysate sodium concentration (150 mEq L(-1)) helps plasma refilling slightly when compared with a normal dialysate sodium concentration (140 mEq L(-1)). However, a high dialysate sodium concentration is associated with a high plasma sodium rebound, which in turn may lead to interdialytic water intake resulting from thirst and may cause increased weight gain and hypertension.     

Thirst and fluid intake following graded hypohydration levels in humans

The relationship among changes in thirst sensations, blood variables, and differential fluid intake in hypohydrated humans was examined. Seven subjects were hypohydrated by 0%, 3%, 5%, and 7% of their body weight on four separate trials which were systematically randomized between subjects. Hypohydration levels were achieved with a regimen of restricted food and fluid intake and moderate heat-exercise stress. Statistically significant linear and quadratic trends were found for the intensity of several sensations with progressive hypohydration levels. In general, plasma osmolality and renin activity increased and plasma volume decreased with increasing hypohydration levels. During a one hour period of ad lib drinking, all subjects consumed insufficient fluid to rehydrate back to baseline body weights. Using regression analyses, fluid intake was predicted by the magnitude of subjective and physiological indices of hypohydration. Results demonstrate that both hypovolemia and plasma osmolality contribute significantly to fluid intake in hypohydrated humans. The results also indicate that thirst sensations make a substantial contribution to differential fluid intake in humans.