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.     

Hypotension and thirst in rats after phentolamine treatment

Administration of the α-adrenergic receptor blocker phentolamine is known to lower arterial blood pressure and to increase renin secretion and water intake in rats. In the present experiments, drinking by rats after subcutaneous administration of the drug was found to be inversely related to arterial blood pressure within the range of 60–90 mm Hg. Drug treatment in nephrectomized rats led to such severe hypotension that drinking was precluded. Pretreatment with propranolol moderated the hypotension in nephrectomized rats and drinking was not attenuated. These results parallel those of previous experiments using the β-adrenergic receptor agonist isoproterenol. Collectively, they suggest that after treatment with these hypotensive agents, a stimulus for thirst can arise from some factor other than angiotensin. This stimulus, perhaps mediated by arterial baroreceptors, is additive in its effects on thirst with the stimulus induced by hypertonic NaCl or subcutaneous colloid treatments.     

Relationships between human thirst, hunger, drinking, and feeding

There is a widely held view that hunger prompts feeding to ensure energy needs are met, while thirst cues drinking to address hydration requirements. However, recent changes in the nature of the food supply and eating patterns have raised questions about the functionality of these relationships with respect to maintaining energy balance. The increasing consumption of energy-yielding beverages and foods with diluted energy density, through the use of ingredients such as high-intensity sweeteners and fat replacers, poses new challenges to presumed homeostatic energy regulatory mechanisms. This review draws on findings from a recent observational study and other published evidence to explore whether shifts of food composition and use patterns may be disrupting relationships between thirst, hunger, drinking, and eating, resulting in positive energy balance (e.g., drinking low satiety, energy-yielding beverages in response to hunger). The observational study entailed collecting hourly appetitive ratings and dietary recalls from 50 adults for seven consecutive days. These data reveal a clear bimodal daily hunger pattern, whereas thirst is stronger and more stable throughout the day. Further, approximately 75% of fluid intake occurs peri-prandially, with the majority derived from energy-yielding beverages. While there is published evidence that drinking is responsive to feeding, support for the view that drinking is the more tightly regulated behavior is stronger. Our data indicates that, due to a number of plausible factors, neither absolute values nor changes of hunger or thirst are strong predictors of energy intake. However, it is proposed that stable, high thirst facilitates drinking, and with the increased availability and use of energy-yielding beverages that have low satiety properties, can promote positive energy balance. There are marked individual differences in mean daily hunger and thirst ratings with unknown implications for energy balance.     

Hunger, thirst and their interactive effects on the rat's drinking in a saccharin-water choice

In a 3 × 3 factorial in which hours of food and water deprivation were varied, Sprague-Dawley rats preferred water to 1.0% saccharin and drank large volumes of it providing hours of water deprivation (thirst), exceeded hours of food deprivation (hunger). All other, i.e. undeprived, equally hungry and thirsty rats, and those whose hunger exceeded thirst preferred 1.0% saccharin but drank small amounts relative to the amounts of water drunk by the thirsty rats. The combined results of this and previous studies employing both choice and single-tube conditions, suggested that thirsty rats drink saccharin primarily for water and to a lesser extent and only with experience, for the sensory stimulation which saccharin provides. Hungry rats drink it primarily for the sensory stimulation. Saccharin in a choice with water seems to provide a means for the determination of the momentarily dominant drive state in naive rats.     

The nature of the thirst stimulus: a factor in conditioned taste-aversion behavior.

Independent groups of rats were compared drinking in response to either water deprivation or osmotic thirst induced by intraperitoneal injections of hypertonic saline. When water or a palatable saccharin solution served as the drinking fluid, deprivation and osmotic thirst produced comparable fluid intakes. In contrast, when a saccharin solution previously associated with the aversive effects of lithium served as the drinking fluid, animals injected with hypertonic saline drank substantially less than water deprived animals. Experiment 2 indicated that this hyperreactivity to a conditioned aversive flavor in animals suffering from osmotic thirst was due to the reduced palatability of the saccharin flavor rather than the previous experience with lithium. Experiment 3 showed that the effect also could not be attributed to differential taste-aversion learning, handling, food deprivation or weight loss before the test sessions. The phenomenon is discussed in terms of various differences between thirst induced by water deprivation and thirst induced by acute cellular dehydration.     

Hypotension and thirst in rats after isoproterenol treatment

Drinking induced in rats by systemic isoproterenol treatment is markedly attenuated after bilateral nephrectomy. The present experiments demonstrate that the hypotension produced by iso-proterenol treatment was more profound, and lasted much longer, in nephrectomized rats than in intact animals. When arterial blood pressure was partially elevated by central administration of angiotensin II or carbachol (Experiment 1) or by intraarterial infusion of epinephrine (Experiment 2), drinking behavior was restored in the nephrectomized animals and their water intakes approximated the amounts consumed by intact rats given isoproterenol. In general, an inverted U-shaped curve was found to define the relation between blood pressure and water intake in rats after isoproterenol treatment. Drinking was most probable when mean arterial blood pressures were in the range of 70–85 mm Hg, whereas rats were unlikely to drink when blood pressures were much below or above this range. These findings indicate that isoproterenol-induced thirst is not dependent on a renal dipsogen, and suggest instead that the hypersecretion of renin that occurs in intact rats is simply permissive of drinking behavior by modulating the hypotensive effects of the drug treatment.     

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.     

Effects of dehydration and rehydration on body temperatures in the black Bedouin goat

 The temperatures of the arterial blood and the brain in black Bedouin goats were measured continuously by miniature data loggers. The animals were either euhydrated or dehydrated to 75–80% of the initial body mass by withholding water for 3–4 days during exposure to intense solar radiation. The daily blood temperature means and maxima of were significantly higher in dehydration than in euhydration, but 40°C was rarely exceeded even during the hot hours of the day. Selective brain cooling occurred in euhydration, but its extent was small when blood temperature was below 39.5°C. In dehydration, however, selective brain cooling was frequent and the standard response when blood temperature exceeded 39°C. We believe that selective brain cooling contributes to the inhibition of evaporative heat loss, which is the primary cause of the higher blood temperature in dehydration. Rapid rehydration with cold water induced long-lasting depression of blood temperature. No evidence was found for mechanisms attenuating the subsequent decrease of brain temperature which occurred a few minutes after the uptake of cold water. Received: 9 March 1998 / Received after revision: 22 May 1998 / Accepted: 30 May 1998     

Apomorphine-induced restoration of drinking to thirst challenges in 6-hydroxydopamine-treated rats.

After bilateral injections of 6-hydroxydopamine along the ascending DA fibers or after lateral hypothalamic electrocoagulation, rats become aphagic and adipsic, and do not drink in response to hypertonic saline or isoproterenol. However, after low doses of the DA-receptor stimulating agent, apomorphine, 6-OH-DA lesioned rats drink near-normal quantities of water in a 30 min test following either regulatory challenge. Apomorphine does not restore drinking to these thirst stimuli in rats with lateral hypothalamic electrocoagulations. These findings (1) provide additional evidence that the ingestive impairments seen after 6-OH-DA injections are due to degeneration of DA-containing neurons, and (2) suggest that the lateral hypothalamic electrocoagulation is functionally different from a specific lesion of DA neurons, possibly by interrupting striatal efferent pathways in addition to the DA afferent fibers. The interruption of these striatal efferents may explain why apomorphine does not restore drinking in the animal with lateral hypothalamic lesions.     

Drinking to intracellular dehydration following vagotomy in rats

Abdominally vagotomized rats maintained on a solid diet drank less and had longer latencies to drink than sham vagotomized rats following IP injection of an osmotic load (0.75 M NaCl, 1% BW). However, these two groups did not differ in latency or water intake following injection of isotonic saline. Since both vagotomized and control rats drank more water and had shorter latencies following injection of hypertonic saline than after isotonic saline, vagotomy apparently attenuated but did not abolish osmotic drinking. Maintenance on a liquid diet and a brief fast prior to testing (to ensure an empty stomach) did not alter these results, indicating that the impairment of gastric emptying of solid food that accompanies total abdominal vagotomy cannot account for the attenuation of osmotically induced drinking. Furthermore, this deficit was seen even when intracellular dehydration was produced at different times during the circadian cycle and when water presentation was delayed 0.5 hr postinjection. In addition, vagotomized rats drank less than control rats following 16-hr water deprivation and exhibited a lower water-food ratio on ad lib regimen. However, vagotomized and sham vagotomized rats exhibited the same relative day-night difference in water consumption as well as short latency response to thermal pain, which with other results indicates that vagotomy did not result in a general impairment of behavior. These findings suggest that osmotic perturbations are detected by the viscera and the information conveyed to the brain via afferent vagus nerves.     

Lipopolysaccharide reduces sodium intake and sodium excretion in dehydrated rats

The objective of this study was to find out if lipopolysaccharide (LPS) administered intraperitoneally affects sodium and water intake and renal excretion in dehydrated rats. LPS (0.3-5 mg/kg b.w.) inhibited 0.3 M NaCl intake induced by subcutaneous injection of the diuretic furosemide (FURO, 10 mg/kg b.w.) combined with the angiotensin converting enzyme inhibitor, captopril (CAP, 5 mg/kg b.w.). Only the highest doses of LPS (2.5 and 5 mg/kg) inhibited water intake induced by FURO/CAP. LPS (0.6 mg/kg) reduced urinary volume and sodium excretion, but had no effect on mean arterial pressure or heart rate of rats treated with FURO/CAP. LPS (0.3-5.0 mg/kg) abolished intracellular thirst and reduced by 50% the urine sodium concentration of rats that received 2 ml of 2 M NaCl by gavage. LPS (0.3-5.0 mg/kg) also reduced thirst in rats treated with FURO alone (10 mg/rat sc). The results suggest that LPS has a preferential, but not exclusive, inhibitory effect on sodium intake and on intracellular thirst. The inhibition of hydro-mineral intake and the antinatriuresis caused by LPS in dehydrated rats may contribute to the multiple effects of the endotoxin on fluid and electrolyte balance and be part of the strategy to cope with infections.     

Lateral preoptic and lateral hypothalamic units: in search of the osmoreceptors for thirst.

Single unit activity was recorded from a variety of brain structures after subcutaneous injection of 16 percent NaCl. Units of the lateral preoptic area (LPO), lateral hypothalamic area (LH) and tractus striohypothalamicus changed activity patterns prior to the behaviorally determined onset of drinking (5.73 min) and had estimated osmolality thresholds less than those associated with the behavioral onset of drinking (1.91 percent). Five distinct activity patterns were recorded for these osmotically sensitive cells. Units from other brain areas either showed no response or responded with activity changes not related to the onset of drinking. The role of LPO and LH cells as osmoreceptors for drinking behavior is discussed.     

Activation of the tubuloglomerular feedback mechanism in dehydrated rats

To study the influence of the tubuloglomerular feedback control (TGF) on the regulation of glomerular filtration rate (GFR) during dehydration, micropuncture experiments were performed on surface nephrons of dehydrated rats. Dehydration was achieved by withdrawal of food and water for 24 h. The urine flow rate decreased to 1.5 μl/min (controls 2.9 μl/min) and GFR decreased in these rats to 0.80 ml/min (controls 1.22). TGF was studied by two different micropuncture procedures. With the first technique the changes in proximal stop-flow pressure in response to changes of the late proximal microperfusion rate were measured. With this technique the perfusion rate necessary to induce a half maximal stop-flow pressure response, the turning point, was also determined. An increased TGF sensitivity was found in dehydrated rats, as indicated by increased stop-flow pressure responses (35 versus 26%) and decreased turning points (16 versus 21 nl/min). With the second micropuncture technique the single nephron GFR (SNGFR) was measured at distal and proximal tubular sites, in the same nephron. Distal SNGFR was decreased during dehydration to 32.2 nl/min, versus 42.7 nl/min in controls. A significant difference between paired SNGFR measurements in the same nephron was observed during dehydration, the proximal value being 5.3 nl/min higher than the distal, whereas this difference was not seen in control rats. This finding indicates that activation of the feedback mechanism takes place to reduce SNGFR. It is concluded that the decrease in whole kidney GFR is partly caused by the observed increase in feedback activity. The present results are also in agreement with our earlier hypothesis that the hydrostatic and oncotic pressure conditions within the interstitial space surrounding the macula densa cells modulate the sensitivity of the tubuloglomerular feedback mechanism.     

Inhibition of drinking by septal stimulation in rats

Bilateral electrical stimulation of the septal forebrain inhibited drinking to extracellular stimuli thought to be mediated, at least in part, by renin-angiotensin. Stimulation at 60 μA but not at 40 μA also inhibited drinking to cellular dehydration. Feeding was not disrupted by either current intensity. The contribution of the septal area to drinking inhibition in rats is discussed.     

Angiotensin II and fluid ingestion in old rats

Fluid ingestion was studied in Fischer 344/Brown Norway F1 rats aged 3, 12, 20, and 24 months of age. There was an age-related decrease in fluid ingestion when fluid intake was measured over 24 h. After water deprivation, 24- and 20-month-old rats drank less than 3- and 12-month-old rats. Twelve, 20-, and 24-month-old rats had less fluid intake associated with food deprivation than did 3-month-old rats. Three month old rats drank more fluid after angiotensin II than did 12-, 20-, and 24-month-old rats when expressed as fluid intake per kg body weight. These studies confirm that the rat is a reasonable model to study age-related hypodipsia.     

The synthesis of amylase in parotid glands of young and old rats

The age-related changes in the rate of synthesis of total and secretory proteins were examined in parotid glands of young (2 months) and old (24 months) rats. The differences in the rate of incorporation of radioactive leucine into acid-insoluble proteins of the gland indicate that the rate of protein synthesis declines with age in this gland. To determine whether the rate of synthesis of secretory proteins changes with age in this gland, the rates of incorporation of [3H]leucine into amylase, a major secretory protein of the gland, were compared by radioactivity determinations. For this comparison, amylase was precipitated with glycogen after incubating the gland slices in the presence of the labeled amino acid. The study shows that rate of synthesis of amylase declines significantly with age in this gland. The possible relationship between the decline in protein synthesis and the reduced level of secretory activity of the gland due to aging is discussed.     

Changes in blood volume and vascular compliance during body heating in rats

The effects of hyperthermia on blood volume and effective vascular compliance were studied in control and heat acclimated rats (three weeks at 32°C and 50% R.H.). Experiments were performed on conscious rats whose abdominal aorta and both jugular veins were cannulated. Continuous changes in blood volume (BV) were monitored by measuring⁵¹Cr tagged erythrocyte dilution, using an arterio-venous extracorporeal shunt passing through a gamma counter. Total vascular compliance was calculated from the relation between changes in BV and central venous pressure during 10 min of infusion of saline at a rate of 1.6% body wt/10 min. Hyperthermia induced a significant blood volume expansion. This expansion was more pronounced in non-acclimated rats. Effective vascular compliance was similar in the normothermic, both nonacclimated and acclimated rats. However, while hyperthermia did not affect the vascular compliance of non-acclimated rats, it was decreased significantly in the acclimated hyperthermic rats. The data suggest that changes in vascular compliance play a role when rapid blood volume changes take place, especially in acclimated hyperthermic animals. The relations between changes in vascular compliance and heat induced redistribution of cardiac output are discussed.     

Drinking by senescent and adult rats in response to regulatory challenges

The regulation of water and electrolyte balance was elevated in senescent (greater than 31 months) and adult (5-10 months) rats of several strains. Weekly food and water intake, drinking induced by 24-hr water deprivation and drinking induced by injection of hypertonic saline were roughly the same in old and adult rats. However, senescent rats drank less after injection of the beta-adrenergic agonist isoprenaline than adult rats. There were no appreciable strain differences in drinking in response to these regulatory challenges although baselines sometimes differed between strains.     

EEG delta power during sleep in young and old rats

Delta EEG power density, which has been viewed as a measure of intensity of NREM sleep, declines across the lifetime in humans, cats, and hamsters, but data in rats have been unclear. It is also uncertain whether older rats differ from younger animals in the degree of change in delta power during recovery sleep following short-term sleep deprivation. We have examined delta power density in NREM sleep under baseline conditions and following 48 h of sleep deprivation in young (3 months), middle-aged (12 months), and older (24 months) rats. The presence or absence of age effects was highly dependent on the method of normalizing the data. When expressed as a fraction of total NREM EEG power, there was no age effect on baseline delta power density, or on the change from baseline to recovery conditions. When expressed as a multiple of delta power in REM under the same condition, the younger rats had higher delta power density than the middle-aged and older rats. For all the ages combined, there was an increase in delta power density in the recovery condition. When examined by age, the younger rats (which started from a higher level of delta power density than the other groups) did not have an increase in delta during recovery; the middle-aged rats tended to, and the older rats (which started from lower baseline levels) significantly increased delta power density in the recovery condition. This suggests that the lower delta power seen during baseline in older rats is not due to decreased ability to generate delta activity.