Drinking caused by exposing dogs to radiant heat.

1. Exposure to radiant heat caused dogs to pant and lose water by evaporation at rates of 40-70 g/hr. 2. When water was offered at intervals during the heating, the dogs drank at about half of the opportunities. The individual drinks were small but, by their repetition, loss of water by evaporation during heating was approximately matched by drinking. 3. Water given by stomach tube reduced drinking during a subsequent period of heating. 4. When water was offered more than 15 min after the end of a period of heating, after panting had ceased, drinking occurred only if the water loss exceeded 50-70 g, about 0-6% of the body water. This is regarded as drinking due to loss of water, beyond a threshold of dehydration necessary to stimulate drinking with the dog at rest. When water was offered during heating, drinking occurred with dehydration less than this threshold. 5. The drinking produced by heating was similar to that produced by running (O'Connor, 1975). When the animal ran under heat, panting was more severe and the water loss greater (85-150 g/hr); it was approximately matched by more drinking.     

Quinine drinking: More regulatory puzzles

Rats were permanently hypodipsic when offered a quinine adulterated fluid on a chronic basis. Plasma osmolarity and Na concentration were normal, but the quinine drinkers showed a slight hyperkalemia compared to water drinking controls. The quinine-drinking rats maintained hydromineral equilibrium through the excretion of a small amount of concentrated urine. The quinine intake was closely matched to need, and fell to near zero when food was removed or water was supplied intravenously. This harmony of intake and output was disrupted after acute hypertonic NaCl load: while the obligatory salt diuresis was no different between water and quinine drinkers, the latter did not drink (except at the lowest level of adulteration) within several hours. However, by 24 hr all had shown a delayed drinking response. This delay in drinking of quinine was also evident after non-painful intravenous NaCl infusions, but no drinking occurred after nephrectomy. Quinine drinkers were also unresponsive to isoproterenol and intracranial dipsogens. These data are discussed in terms of their implication for definitions of regulatory drinking behavior.     

Gastric distention and thirst: Relevance to the osmotic thirst threshold and metering of water intake

The osmotic reactivity of the thirst mechanism was measured in dogs when gastric distention was started immediately before intravenous infusion of 5% NaCl, simultaneously with the infusion, and 10–20 or 30–40 min prior to it. Volume of water drunk after 30, 60 and 120 min of the infusion was measured. The effects of distention of the stomach was also determined during drinking and the size of single draughts as well as the cumulative amount of water drunk during 25 min of 5% NaCl infusion were measured. Gastric distention did not influence the osmotic thirst threshold. It was similar independently of the time at which the 5% NaCl infusion was initiated. Total water intake did not change after hypertonic saline infusion; however, gastric distention prolonged the time in which the dogs usually completed drinking (30 min) up to 2 hr. Distention of the stomach during drinking neither interrupted water intake nor changed the pattern of drinking during the hypertonic saline infusion. These results question the role of gastric stretch receptors in the drinking response.     

Postingestional modulation of drinking induced in rats by angiotensin II: intragastric infusion and sham drinking studies

The dipsogenic potency of angiotensin II (ANGII, 200 micrograms/kg, SC) was examined after the removal of various postingestional factors. In the first experiment, rats with intragastric catheters were injected SC with ANGII and allowed water to drink. During the induced drinking, either NaCl (1.5 M) or water was injected into the stomach via the catheter at a rate of 0.1 ml for each ml water ingested orally. The water intake was identical in the two conditions. In a second experiment, rats, fitted with gastric fistulas, were administered ANGII and subsequent water intake with fistulas open was compared to that occurring with the fistulas closed. Rats drank more water during the first trial with fistulas open than with fistulas closed. Water intake during subsequent trials with an open fistula rose above that observed on the first trial. In a third experiment, rats with gastric fistulas were offered 0.15 M NaCl to drink. Intake was greater when the fistula was open than when it was closed. Intake of 0.15 M NaCl increased during the second trial with fistula open. Rats drank more 0.15 M NaCl during the first trial with an open fistula in Experiment 3 than those rats given water to drink on their first trial with fistula open in Experiment 2. These data suggest both oropharyngeal and postingestional factors interact in the control of ANGII-induced fluid intake.     

Gastric emptying and intestinal absorption of ingested water and saline by hypovolemic rats

Recent experiments showed that in a one-bottle test conducted 16 h after sc injection of polyethylene glycol (PEG) solution, hypovolemic rats consumed water or 0.30 M NaCl in an initial drinking episode but did not empty the ingested fluid from the stomach or absorb it from the small intestine very rapidly, certainly not as rapidly as when 0.15 M NaCl was consumed (Smith et al., Am J Physiol 292: R2089-R2099, 2007). The present experiments examined the patterns of water and 0.30 M NaCl ingestion and the movement of consumed fluid through the gastrointestinal tract when PEG-treated rats were given a two-bottle delayed-access test. We found that both fluids always were consumed in the first drinking episode, that the fluid mixture ingested was equivalent to 0.10-0.15 M NaCl, and that gastric emptying rate and net fluid absorption from the small intestine usually were much faster than when PEG-treated rats drank either water or hypertonic saline alone. Thus, ingestion of water and 0.30 M NaCl by hypovolemic rats in the same episode adaptively facilitated the movement into the circulation of a near-isotonic fluid that is ideal for restoring plasma volume deficits.     

Increased drinking of a nonpreferred NaCl solution during food deprivation in the C3H-HeJ mouse

When food was given ad lib, C3H/HeJ mice showed a progressive decrease in NaCl solution intake as the concentration increased from 0.5–2.5% under single tube or double tube conditions. Under the latter condition, 1.5% NaCl intake volumes were approximately 20% of water intake volumes. However, when restricted to $\text{1}\text{3}$ normal food intake, the mice showed significant increase in the intake of 1.5% NaCl and several animals consumed more salt solution than water. Salt intakes declined to predeprivation levels upon return to free feeding. Since feeding of a sodium deficient diet produced no alteration in intake of 1.5% NaCl, the increase during food deprivation was attributed to hypovolemia rather than hyponatremia.     

Pre-exposure to wheel running disrupts taste aversion conditioning

When rats are given access to a running wheel after drinking a flavored solution, they subsequently drink less of that flavor solution. It has been suggested that running produces a conditioned taste aversion (CTA). This study explored whether CTA is eliminated by prior exposure to wheel running [i.e., unconditioned stimulus (UCS) pre-exposure effect]. The rats in the experimental group (UW) were allowed to wheel run for 1 h daily for seven consecutive days of pre-exposure. Rats in the two other groups had either access to locked wheels (LW group) or were maintained in their home cages (HC group) during the pre-exposure days. All rats were then exposed to four paired and four unpaired trials using a "ABBAABBA" design. Conditioning trials were composed of one flavored liquid followed by 60-min access to wheel running. For the unpaired trials, rats received a different flavor not followed by the opportunity to run. All rats were then initially tested for water consumption followed by tests of the two flavors (paired or unpaired) in a counterbalanced design. Rats in the UW group show no CTA to the liquid paired with wheel running, whereas LW and HC groups developed CTA. These results indicate that pre-exposure to wheel running (i.e., the UCS), eliminates subsequent CTA.     

Regulation of NaCl solution intake and gastric emptying in adrenalectomized rats

Adrenalectomized (adrex) rats adaptively increase NaCl intake to compensate for the uncontrolled loss of Na(+) in urine due to the absence of aldosterone. After a period of NaCl deprivation, they ingest saline avidly but stop drinking before hyponatremia is repaired. The present experiments determined whether pre-systemic signals inhibit further NaCl intake, and whether gastric emptying of Na(+) is modulated according to the concentration of ingested NaCl solution. After overnight deprivation, adrex rats consumed 0.05 M and 0.15 M NaCl at a maximally fast rate ( approximately 1.7 ml/min) and emptied ingested fluid from the stomach at a slower but maximally fast rate ( approximately 1.1 ml/min). When 0.30 M NaCl was consumed instead, fluid intake still was maximally fast but gastric emptying slowed in proportion to concentration so that the emptying of Na(+) was comparable to that observed when 0.15 M NaCl was ingested ( approximately 0.13 meq/min). When 0.50 M NaCl was consumed, intake slowed proportionately so that Na(+) consumption was comparable to that observed when 0.30 M NaCl was ingested ( approximately 0.5 meq/min). NaCl intake appeared to be inhibited both by the concentration of saline emptied from the stomach and by the volume of ingested fluid in the stomach and small intestine. Gastric emptying also slowed proportionately when 0.50 M NaCl was consumed, as if the rats were regulating the delivery of Na(+) to the small intestine. These results suggest that adrex rats can detect the volume and concentration of ingested NaCl solution presystematically and integrate these two variables, and thereby modulate the rates of Na(+) intake and gastric emptying.     

Drinking in the pigeon (Columba livia) in response to water deprivation and the influence of intracerebroventricular infusions of NaCl or sucrose solutions

Pigeons were deprived of fluid for 24 hours then allowed access to water and a 2.7% NaCl solution, the intakes of both solutions during the subsequent 60 min were observed. In a second experiment hypertonic or isotonic solutions of NaCl or sucrose were infused ICV, starting 5 min before access to the solutions and finishing 10 min after access, and the consummatory behaviour observed. Pigeons rehydrated themselves after the period of deprivation with a volume of water equal to the weight lost during the deprivation. Pigeons never drank the hypertonic NaCl solution. ICV infusions of hypertonic or isotonic sucrose attenuated drinking in response to 24 hours water deprivation. Isotonic or hypertonic NaCl infused ICV, on the other hand, had no significant effect. Thus, in the pigeon, drinking in response to 24 hours of water deprivation appears to be controlled by one mechanism, possibly osmoreceptor in nature (with the permissive control of CSF sodium concentration), since the birds drank a volume of water equal to their weight loss and changes in CSF sodium concentration influenced drinking in a manner similar to that described previously for osmotically induced drinking in pigeons.     

The voluntary correction of sodium deficiency by the rabbit

The behaviour involved in the correction of sodium deficit has been studied in wild rabbits and also laboratory bred rabbits. They were offered 0.5 M NaCl to drink. In adrenalectomized wild rabbits variable sodium deficits were produced by withdrawal of mineralocorticoid for 24-72 hr. Correction of the deficit was remarkably precise and was achieved in 9-24 hr, being slower with smaller deficits. That is, the rate of drinking was almost commensurate with the degree of body deficit. No overdrinking occurred by 24 hr. Repetition of the experiment with 24 hr deficiency and with the offer of a cafeteria of 0.5 M NaCl, 0.5 M KCl, 0.25 M CaCl2 and 0.25 M MgCl2 showed the increased appetite was specific for NaCl. Both wild and laboratory rabbits, adrenally intact, were made sodium deficient by the diuretic furosemide. Voluntary salt intake did not peak until 6-12 hr later reflecting the characteristic delay in the genesis of salt appetite. If presentation of salt were delayed 24 hr after furosemide, the highest rate of intake was seen immediately in both wild and laboratory rabbits, but the wild rabbits were much faster in fully correcting body deficit. Infusion of isotonic NaCl, adequate to correct the deficit, given during the third-sixth hour of access to NaCl under the 24 hr delay of presentation regime, halved salt appetite over this period, and by 9-12 hr it was abolished. Polyethylene glycol induced subcutaneous fluid sequestration, salt appetite and thirst but caused an obvious severe deterioration in the animals condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in blood pressure and muscle sympathetic nerve activity during water drinking in humans

To investigate the possible involvement of the sympathetic nervous system in pressor response during water drinking, muscle sympathetic nerve activity (MSNA), blood pressure (BP), and heart rate (HR) were continuously measured in healthy young volunteers throughout the experiments of a 5-min control, 2 min of drinking 500 ml water, and a 28-min recovery. To avoid the effects of water passing through the oropharyngeal and esophageal regions and/or effects of swallowing, an equal amount of water was directly infused to the stomach through a stomach tube for 2 min. Water drinking caused a transient increase in mean arterial pressure (MAP) and HR immediately after drinking (DeltaMAP, 12.6 +/- 2.1 mmHg; DeltaHR, +19.9 +/- 1.7 beats/min at the peak). An abrupt decrease of MSNA was observed directly during water drinking (Deltaburst rate, -6.9 +/- 1.3 bursts/min; Deltatotal activity, -2,606 +/- 491 U/min), and it increased to the baseline level thereafter. Gastric infusion had little or no effect on MAP, HR, and MSNA. The present study demonstrated that a pressor response during water drinking was associated with the attenuation of MSNA and not generated by gastric infusion of water at the same rate as in this drinking manner. In conclusion, the rapid rise in BP might be caused through stimulations from the oropharyngeal region, swallowing-induced factors, and/or a feedforward mechanism by a central descending signal from the higher brain centers.     

Flavor-toxicosis associations: tests of three hypotheses of long delay learning

Rats were prepared with gastric cannulas and esophageal fistulas to assess the contribution of taste and smell, postingestinal stimuli, and the combination of the two in forming flavor-toxicosis associations. Groups were either given sugar water to drink, a stomach intubation of sugar water, both sugar water to drink and a stomach intubation of sugar water, or not given sugar water. The experimental and pseudo-conditioning control animals were given a LiCl injection and the control animals were given a NaCl injection one hour later. They were tested for drinking of sugar water the next day. It was found that taste and smell are the primary stimuli for forming food aversions. Furthermore, postingestional stimuli are not sufficient to produce this type of learning.     

Recovery from disordered drinking by vagotomized rats.

Within 8 weeks after bilateral subdiaphragmatic vagotomy, rats failed to respond to 3 stimuli of thirst: water consumption in absence of food, cellular dehydration produced by hypertonic NaCl, and beta-adrenergic activation using isoproterenol. Sixteen weeks post-surgery, however, these deficits in drinking behavior disappeared. Eight weeks after surgery, for example, following intragastric loads of 5% NaCl at 1 ml/100 g body weight, vagotomized rats drank 2.3 ± 0.3 ml water; their sham-operated controls drank 17.4 ± 1.6 ml. The corresponding values 16 weeks post-surgery were 17.4 ± 0.7 for the vagotomized rats and 17.9 ± 0.7 ml for the laparotomized controls. When isoproterenol (0.05 mg/100 g) was injected, for the initial tests vagotomized rats and their controls drank 3.2 ± 0.3 ml and 15.8 ± 0.8 ml water, respectively, and the corresponding values 16 weeks post-surgery were 15.8 ± 0.7 ml and 14.9 ± 0.7 ml, respectively. There was no recovery of efferent vagal function so recovery of drinking was probably not due to nerve regeneration.     

Inhibition of thirst in rats following hypovolemia and-or caval ligation

Thirst was elicited in rats by subcutaneous injections of a hyperoncotic polyethylene glycol (PG) solution or by infrahepatic ligation of the inferior vena cava (IVC). Rats given either treatment drank throughout the 24 hr test period when 0.15 m NaCl was the only fluid available but decreased drinking significantly within 6–8 hr when given only water. This inhibition of thirst was associated with an excessive accumulation of ingested water during oliguria. Inhibition cannot be attributed to a general osmotic dilution since plasma osmolalities actually were elevated due to the retention of urea. Instead, the inhibitory mechanism may involve reduction of the effective osmotic pressure of body fluids and cellular overhydration. Rats drinking water following combined IVC ligation and PG injection treatments required a greater degree of cellular overhydration to inhibit drinking than rats given either treatment alone. When saline was presented instead of water, the complex stimulus for thirst elicited more drinking with fluid retention than any other experimental procedure known. The extreme potency of this preparation reflects the comparable strength of the inhibitory mechanisms associated with cellular overhydration.     

Cellular and extracellular dehydration, and angiotensin as stimuli to drinking in the common iguana Iguana iguana.

1. After water deprivation, the iguana promptly drank slightly more than enough water to restore the body fluids to isotonicity even under conditions of hypervolaemia. 2. In response to systemic injections of hypertonic solutions of NaCl and sucrose, the iguana drank and retained enough water to dilute the injected load to isotonicity irrespective of whether water was offered immediately or after 3 hr, and irrespective of whether the solute was administered I.V. or I.P. 3. Hypertonic solutions to glucose, urea, sorbitol and KCl caused little drinking. 4. The long latencies to drinking after hypertonic loads, which were not dependent on the nature of the solute, the route of administration or the dosage, were shown not to be a result of slow distribution of the solute throughout the body fluids. 5. Clearance of injected solutes via renal and extra-renal (nasal salt gland) routes was negligible during the 6 hr experimental period. 6. Measurements of plasma [Na], haematocrit, osmotic pressure and inulin space showed that the iguana drank, in response to cellular dehydration, enough water to restore the intracellular fluid volume to normal. 7. We conclude that, in response to substances which dehydrate cells, the iguana regulates its body osmolality precisely and efficiently provided it is able to do so by drinking. In this respect the responses of the iguana are similar to those of the nephrectomized rat since, in the short term, both rely exclusively on drinking to restore cellular water to normal. 8. The iguana also drinks in response to extracellular dehydration produced by hyperoncotic peritoneal dialysis, and in response to I.P. angiotensin II.     

Learning and meal-associated drinking: meal-related deficits produce adjustments in postprandial drinking

Two experiments examined the effect of meal-related water deficits on the distribution of meal-associated drinking. In the first procedure free-feeding rats received 10-, 20-, or 30-min delays between the end of a meal and the subsequent availability of postprandial water. Each delay condition remained in effect for 10 consecutive days. The primary effect of the delay was to postpone the intake of postprandial drinking. None of the delay conditions produced an increase in preprandial drinking. However, when the rats were returned to baseline following the delay conditions a pronounced rebound effect was obtained in the proportion of postprandial drinking. The second experiment followed the same general procedure except that 5-min access to water was always presented after each meal and before the postprandial water restrictions. Under this procedure the rats increased their water intake during the 5-min period when the postprandial restrictions were imposed. These findings show that meal-related water deficits can affect the timing and proportion of postprandial drinking, but provide no evidence that meal-related deficits increase preprandial drinking. The results suggest that the anticipation of meal-related water deficits may play a role in shaping the rat's postprandial drinking pattern.     

Inhibition of compensatory renal growth in rats

1. Compensatory renal hypertrophy in unilaterally nephrectomized rats was measured by estimation of dry weight, protein content, RNA and DNA changes and rate of oxygen consumption. Inulin clearances (= GFR) and water and solute excretions were estimated in animals given by stomach tube either 5 ml. water or 5 ml. 0.6% NaCl solution/100 g body wt.2. Kidneys removed when animals were unilaterally nephrectomized were homogenized in 0.25 M sucrose and fractions containing mitochondria or microsomes were obtained by centrifugation. Renal cortex and medulla were similarly treated.3. Intraperitoneal injections of microsomes and/or supernatant fluid from a kidney homogenate or from the renal cortex usually inhibited compensatory growth of the contralateral kidney and prevented any increase of its protein content.4. Injections of microsomes and/or supernatant fluid from the renal medulla had no significant effect on the rate of compensatory hypertrophy.5. After I.P. injection of microsomes and supernatant fluid from a homogenate from the renal cortex there was no rise of the RNA/DNA ratio in the contralateral kidney and the rate of oxygen uptake of its cortex decreased, while that of anaerobic glycolysis increased.6. Injections of microsomes and supernatant fluid from kidney homogenate did not affect glomerular filtration rate which increased as in control unilaterally nephrectomized rats.7. In unilaterally nephrectomized rats, injected with microsomes and supernatant fluid from a kidney homogenate, there was a decrease of osmolal clearance, in spite of the raised glomerular filtration rate. The decrease of osmolal clearance lasted for several days, and was most pronounced when the animals had been given by stomach tube 5 ml. 0.6% NaCl solution/100 g body wt.     

Rescue of the mineralocorticoid receptor knock-out mouse

The mineralocorticoid receptor knock-out mouse (MR–/–), resembling inborn pseudohypoaldosteronism, dies 8–12 days after birth in circulatory failure with all the signs of terminal volume contraction. The present study aimed to examine the functional defects in the kidney and colon in detail and to attempt to rescue these mice. In neonatal (nn) MR–/– the amiloride-sensitive short-circuit current in the colon was reduced to approximately one-third compared to controls (MR+/+ and MR+/–). In isolated in vitro perfused collecting ducts the amiloride-induced hyperpolarization of the basolateral membrane (V _bl) of nn MR–/– was similar to that of controls, but urinary Na⁺ excretion was markedly increased to 4.3 μmol/day·g (BW). Based on this measured urinary Na⁺ loss we tried to rescue nn MR–/– mice by injecting NaCl twice daily (3.85 μmol/g BW), corresponding to 22 μl of isotonic saline/g BW subcutaneously. This regimen was continued until the animals had reached a body mass of 8.5 g. Thereafter, in addition to normal chow and tap water, NaCl drinking water (333 mmol/l) and pellets soaked in 333 mmol/l NaCl were offered. Unlike the untreated nn MR–/– most of these mice survived. The adult animals were examined between days 27 and 41, some were used for breeding. When compared to age-matched controls the growth of MR–/– was delayed until day 20. Then their growth curve increased in slope and reached that of controls. MR–/– retained their Na⁺-losing defect. Amiloride’s effect on urinary Na⁺ excretion was not significant in MR–/– mice and the effect on V _bl in isolated cortical collecting ducts was attenuated. The renin-producing cells were hypertrophic and hyperplastic. Plasma renin and aldosterone concentrations were significantly elevated in MR–/– mice. These data indicate that MR–/– can be rescued by timely and matched NaCl substitutions. This enables the animals to develop through a critical phase of life, after which they adapt their oral salt and water intake to match the elevated excretion rate; however, the renal salt-losing defect persists. Received: 22 February 1999 / Received after revision and accepted: 29 March 1999     

Effects of N-acetylcysteine on fetal development and on phenytoin teratogenicity in mice

The teratogenicity of phenytoin may result from its enzymatic bioactivation to a reactive intermediate, which interacts irreversibly with fetal tissues. Since glutathione (GSH) is involved in the detoxification of many reactive intermediates, N-acetylcysteine (NAC), a glutathione precursor, was evaluated for its effects on murine fetal development and phenytoin teratogenicity. NAC, 100 to 275 mg/kg, was given intraperitoneally (ip) or per os (po), or as 266 to 410 mg/kg in the drinking water, at various times before or after phenytoin, 65 to 75 mg/kg ip, on gestational days 12 and 13. Dams were killed on gestational day 19, fetal resorptions were noted, and fetuses were examined for anomalies. Significant reductions in phenytoin-induced fetal weight loss and cleft palates were observed when NAC was given by gavage 6 hours after phenytoin or in the drinking water with the lower dose of phenytoin. NAC administered in the drinking water also reduced the incidence of resorptions produced by the higher dose of phenytoin and enhanced postpartum survival in fetuses exposed to 65 or 75 mg/kg phenytoin (P less than .05). Conversely, the incidence of resorptions increased when NAC was given by gavage at other times before or after phenytoin, by single or repetitive ip injections, or in high concentrations in the drinking water (P less than .05). When given with the higher dose of phenytoin, NAC administered via the drinking water significantly increased the incidence of phenytoin-induced cleft palates and fetal weight loss (P less than .05). Similar results were obtained with a single ip injection of NAC and a lower dose of phenytoin. Thus, when given orally, NAC can partially reduce phenytoin teratogenicity and embryopathy. However, altering the route of NAC administration, or increasing the dose of phenytoin and/or NAC, enhanced phenytoin embryotoxicity, and NAC alone at higher doses had embryopathic effects.     

Decontamination of gnotobiotic mice experimentally monoassociated with Candida albicans.

Gnotobiotic AKR mice, experimentally monoassociated with Candida albicans, were successfully decontaminated by oral treatment with amphotericin B incorporated in the drinking water. Germfree mice first were swabbed orally with viable C. albicans and then were allowed to acclimatize for 4 weeks. The log10 of number of C. albicans per gram of organ (with luminal contents) was 7.9 and 7.7 in the stomach and cecum, respectively. Direct fecal smears, as well as impresssion smears of stomach and cecum mucosal surfaces, revealed yeastphase cells, many with germ tubes, but no hyphal forms. No illness or mortality was observed over this period. The mice then were given amphotericin B DISsolved in the drinking water and offered ad libitum. At levels of 0.1 and 0.2 mg/ml, the number of fecal C. albicans was decreased but not eliminated completely. However, 0.3 mg/ml was sufficient to decontaminate the mice completely and return them to the germfree state. Residual amphotericin B was detected in the feces of the mice only while they were receiving the 0.3 mg/ml dose level. These mice remained germfree until the termination of the experiment, 10 weeks after the antibiotic had been discontinued and replaced by plain drinking water.