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Thirst and salt appetite induced by hypovolemia in rats: analysis of drinking behavior.

A detailed description of the increased intake of water and 0.5 M NaCl solution by rats after colloid-induced hypovolemia was obtained by measuring drinking activity every 6 s for 23 h. After an initial phase of largely single-bout water drinking that reflected hypovolemic thirst, there was a marked increase in saline drinking in multiple-bout episodes. This salt appetite developed while rats were volume depleted but persisted for hours even after the plasma volume deficits were repaired. Their drinking episodes then seemed to reflect osmoregulation, since cumulative intakes of water and saline were in appropriate proportions to produce a near-isotonic NaCl solution. Remarkably, rats concocted a 1% NaCl solution within 29% of the drinking episodes, by alternating intakes of water and saline every 30-90 s. This alternation was too rapid to allow significant absorption of ingested fluids from the intestines and changes in plasma osmolality, and thereby to permit central osmoreceptors to influence ongoing consumption. Instead, we propose that, in these episodes, rats are guided by gustatory receptors to obtain the desired NaCl in a palatable solution.

Angiotensin II↗

Interactive dopaminergic and noradrenergic systems in the regulation of thirst in the rat.

Twenty-three hours of fluid deprivation led to elevated plasma levels of corticosterone and free fatty acids, as well as increased whole brain dopamine levels, in rats. Drinking could be initiated in water-replete rats by administration of single doses of the dopamine agonist, pergolide, the dopamine beta-hydroxylase inhibitor, diethyldithiocarbamate, the alpha-adrenergic antagonist, phenoxybenzamine, or the beta-adrenergic agonist, isoproterenol. In each case, the response to these agents was reduced or ameliorated by cotreatment with the dopamine antagonist, pimozide. Taken together, the results of the stress and pharmacological studies support the concept that drinking is initiated by a dopaminergically mediated thirst drive, which in turn is regulated by a noradrenergically mediated satiety system.

Adrenal Glands↗

Water deprivation, plasma osmolality, blood volume, and thirst in young pigs.

When deprived of both drinking water and food, pigs failed to develop the hyperosmolality usually expected with dehydration. In further studies 12 pigs were deprived of drinking water and food, and the effects were compared with data from nondeprived pigs, pigs water deprived but with food available, and pigs with water but no food. When food was eaten during water deprivation, plasma osmolality rose to levels sufficient to stimulate drinking. During water and food deprivation, plasma osmolality failed to rise, even over 24 h, and usually fell. Blood volume changes were calculated from packed cell volume and plasma protein data, and it was found that blood volume fell significantly when both food and water were withheld, but not when only water was withheld. It appears that the conditions of deprivation determine the proportions of thirst stimulation that can be attributed to plasma hypertonicity and to hypovolemia.

Animals↗

Anteroventral third ventricle site of action for angiotensin induced thirst.

The central site of action for angiotensin induced thirst was investigated in rats. Subfornical organ lesions resulted in a temporary abolition of drinking induced by lateral preoptic or lateral ventricle microinjections of angiotensin but drinking to anteroventral third ventricle microinjections of angiotensin (or carbachol) was unaffected. Drinking to elevated systemic levels of angiotensin was attenuated but not abolished by subfornical organ lesions. When spread of injected angiotensin via cerebrospinal fluid circulation was controlled by placing plugs at selected locations in the ventricles, drinking was elicited only when intracranial microinjections of angiotensin gained access to anteroventral third ventricle. It was concluded that subfornical organ is not the exclusive dipsogenic receptor for angiotensin, rather angiotensin exerts at least part of its dipsogenic effect by spread through the ventricular system to receptors in the vicinity of the anteroventral third ventricle.

Angiotensin II↗

Effect of an angiotensin antagonist, Sar1-Ala8-angiotensin II on physiological thirst.

Initially it was shown that infusion of Sar1-Ala8-angiotensin II (P113) into the third ventricle (50-100 mug/ml at 1.1 ml/hr) effectively abolished the large water intake induced 1-2 min after beginning an intracarotid infusion of angiotensin II at 800 ng/min which causes an unphysiologically high concentration of angiotensin II in cerebral arterial blood. Infusion of P113 (50-100 mug/ml at 1.1 ml/hr) into the third brain ventricle for 20 min prior to and during presentation of water to sheep after 48 hr water deprivation did not reduce water intake. Water intake associated with rapid food intake or carotid artery infusion of hypertonic NaC1 was similarly unaffected by intraventricular administration of P113. While high concentrations of angiotensin II are dipsogenic in sheep, these results cast doubt on a contributory role for angiotensin II in thirst caused by water depletion or rapid food intake in the sheep.

Angiotensin II↗

Prostaglandin E1 inhibits acute cell dehydration thirst.

Intraperitoneally injected PGE1 (100 micrograms/Kg) inhibits specifically the drinking induced by both IP and IV 2 M NaCl (6 ml/Kg) and compound 48/80 (100 micrograms/Kg, IP). Probenecid (150 mg/Kg, IP) which is not a dipsogen, has no effect on the PGE1 induced inhibition of acute cell dehydration thirst. It is concluded the PGE1 acts upon the peripheral mast cells, inhibiting their secretion and thus affecting the water intake associated with the activation of these cells either by hypertonicity or specific stimulants of amine release. These results raise the possibility that endogenous prostaglandins might be involved in the modulation of some of the signals which convey to the brain information on the tonicity of the body fluids.

Animals↗

Schedule-induced drinking and thirst: a pharmacological analysis.

Similar levels of water consumption were induced in two groups of rats by means either of prior fluid deprivation or a schedule of food pellet delivery. Injections of d-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg) had similar attenuating effects of drinking induced by both procedures. Chlordiazepoxide (2.5, 5.0, 10 and 20 mg/kg), however, exerted differential actions on schedule-induced and deprivation-induced drinking. Drinking induced by deprivation was facilitated by all doses of this drug while the higher doses decreased levels of schedule-induced drinking. This result emphasises the difficulties involved in using the concept of thirst in explanations of behavior and of drug action.

Animals↗

Periventricular preoptic-hypothalamic lesions: effects on isoproterenol-induced thirst.

Lesions of the periventricular tissue surrounding the anteroventral third ventricle (AV3V) have been shown to block the dipsogenic properties of many experimental manipulations, including injections of angiotensin. The present study examines the ability of rats with ablations of the AV3V to initiate drinking responses following administrations of isoproterenol, a beta-adrenergic agonist which is thought to elicit drinking in part by activating the peripheral renin-angiotensin system. It was found that rats bearing lesions of the AV3V region drank significantly less across a range of doses than animals with sham lesions. When taken together with results from other studies, the present findings suggest that destroying the AV3V region inhibits the thirst-including properties of endogenous, as well as exogenous angiotensin.

Animals↗

Thirst in the rat after ligation of the inferior vena cava: role of angiotensin II.

The role of angiotensin II in thirst states after ligation of the inferior vena cava above (CLA) or below (CLB) the origin of the renal veins as compared to sham operated controls was evaluated 24 hrs after ligation. Water intake was enhanced in CLB rats and even more so in CLA rats. Plasma angiotensin II and urea concentrations and serum osmolality were increased in CLA rats. Plasma sodium concentration and hematocrit were reduced in CLA rats, and hematocrit in CLB rats as well. Water intake in CLA rats was retarded by IV infusions of saralasin. Saralasin infusions in CLA rats resulted in a dramatic increase of plasma angiotensin II concentrations. Ligation of the inferior vena cava induces major changes in body fluid homeostasis, which are more pronounced in CLA than in CLB rats. The increase in water intake in CLA rats appears to be partly mediated by angiotensin II.

Angiotensin II↗

Interaction of vasopressin and angiotensin II in central control of blood pressure and thirst.

It is now well recognized that systemically released angiotensin II (Ang II) and arginine vasopressin (AVP) act in concert in regulation of blood pressure and water-electrolyte balance. Numerous studies have also demonstrated that centrally applied Ang II and AVP cause significant alterations of the cardiovascular functions and body fluid balance. Moreover, it has been established that Ang II and AVP are released in the central nervous system during cardiovascular and osmotic disorders and that the cardiovascular regions of the brainstem and the osmoregulatory regions of the forebrain are extensively innervated by the angiotensinergic and vasopressinergic neurons. Some evidence indicates that the angiotensinergic and vasopressinergic system may interact in the central blood pressure control, although the significance of this interaction may differ in various species. Recently, attempts have been made to find out whether centrally released Ang II and AVP may play a role in the regulation of the cardiovascular system under physiological and pathophysiological conditions. With regard to this, the available evidence strongly suggests that the both systems may be involved in regulation of blood pressure under baseline conditions. In addition, the vasopressinergic system appears to be involved in the adjustment of cardiovascular functions to hypovolemia, whereas its role in regulation of blood pressure during the osmotic disorders is less clear. Regulation of blood pressure and heart rate by centrally released AVP under baseline conditions, during hypovolemia and in osmotic disorders is significantly altered in the spontaneously hypertensive rats. It is now well established that centrally applied Ang II and Ang III are potent dipsogenic compounds. There also is evidence that AVP may enhance the osmotic thirst. However, the physiological role of brain-derived AVP and Ang II in the control of water intake awaits further examination. The available evidence from rat studies does not give support to a significant cooperation between central angiotensinergic and vasopressinergic system in regulation of water intake.

Angiotensin II↗

Effects of oral, intraperitoneal and intrajugular rehydrations on water retention, rumen volume, kidney function and thirst satiation in goats.

1. In order to test the hypothesis that peripheral receptors are involved in the control of fluid re-distribution following acute dehydration and rapid rehydration, peripheral rehydrations (oral or intraperitoneal) were compared with central (intrajugular) rehydration. 2. The experiments were carried out with four goats dehydrated to about 20% of their initial mass. 3. Following peripheral rehydration, a higher proportion of water was retained in comparison with central rehydration, and this was related to a more effective kidney retention mechanism, i.e. lower GFR and higher tubular reabsorption. 4. Higher proportions of water were retained in the rumen in the peripheral rehydrations in comparison with the central one apparently due to increased saliva secretion. 5. Thirst saturation was more effective with the peripheral rehydration in comparison with the central one and was related to the amount retained in the rumen and to peripheral blood expansion (or dilution).

Animals↗

The association of thirst, sodium appetite and vasopressin release with c-fos expression in the forebrain of the rat after intracerebroventricular injection of angiotensin II, angiotensin-(1-7) or carbachol.

The effect intracerebroventricular injections of angiotensin II (0.1 nm), angiotensin-(1-7) (1 or 100 nm) and carbachol (500 ng) on c-fos expression was examined in the forebrain of Lister hooded rats. Intense staining of the c-Fos protein was found in the median preoptic nucleus, organum vasculosum of the lamina terminalis, subfornical organ, paraventricular nucleus and supraoptic nucleus after angiotensin II and carbachol Angiotensin II caused significantly more c-fos expression in the ventral median preoptic nucleus and organum vasculosum of the lamina terminalis than carbachol, whereas in the paraventricular and supraoptic nuclei this was reversed, with carbachol having a greater effect on c-fos expression in these areas. Angiotensin-(1-7), however, only induced c-Fos protein in the organum vasculosum of the lamina terminalis and median preoptic nucleus with the number and the intensity of staining of the nuclei significantly less in both areas than after angiotensin II or carbachol. Separate groups of Lister rats were given i.c.v. injections of the same substances at the same doses, but excluding the lower dose of angiotensin-(1-7), and the intakes of water and 1.8% NaCl over 60 min were measured. Angiotensin II stimulated intakes of both water and NaCl. The effect on water intake was almost immediate (<1 min), whereas NaCl intake did not usually start until at least 5 min after injection. Over 60 min, water (12.4 +/- 1.0 ml) and NaCl (4.2 +/- 0.9 ml) intakes were significantly greater than water (1.1 +/- 0.2 ml) and NaCl (0.6 +/- 0.5 ml) intakes of the controls. Carbachol caused less drinking than angiotensin II, the water intake over 60 min being significantly less (4.8 +/- 0.7 ml) and the latency of response greater (>5 min). Carbachol, unlike angiotensin II, had little effect on NaCl intake (0.7 +/- 0.4 ml). Angiotensin-(1-7) had no effect on water (1.1 +/- 0.3 ml) or NaCl (0.3 +/- 0.3 ml) intakes. The plasma levels of vasopressin were measured after i.c.v. injection of the same three substances in the same doses, again excluding the lower dose of angiotensin-(1-7), in further groups of rats. Angiotensin II and carbachol caused an approximate five-fold increase in plasma vasopressin levels compared to cerebrospinal fluid-injected rats, but angiotensin-(1-7) had no effect on vasopressin release. Therefore, three compounds with widely differing effects on thirst, sodium appetite and vasopressin release induce distinctive patterns of c-fos protein expression in the forebrain. By combining experimental approaches in this way it is possible to determine areas of the brain which are involved in certain behavioural and endocrine responses.

Angiotensin I↗

Lateral preoptic neurons inhibit thirst in the rat.

Kainic acid (KA) and muscimol were injected into the lateral preoptic area (LPO) of the rat to study their effects on drinking behavior. A low dose (5 ng) of KA, which stimulates neurons, decreased the amount of water intake induced by hypertonic saline (IP) and angiotensin II (SC). Injection of 2 ng muscimol, a potent GABAA receptor agonist that suppresses neurons, facilitated drinking responses induced by hypertonic saline, but did not affect angiotensin II-induced drinking. Rats injected with a high dose (150 ng) of KA, which destroys neurons, showed marked polydipsia accompanied by increased urination. One week after the KA lesion, drinking and urine output recovered to normal. During the polydipsia, a small volume of concentrated urine could be excreted if water intake was restricted. After recovery, excessive drinking responses followed water deprivation and hypertonic saline load. The rats normally drank water in response to angiotensin II and to polyethylene glycol solution. The results show that activation of LPO neurons inhibits water intake, and that suppression of LPO neurons facilitates osmotically induced water intake. Therefore, LPO neurons are probably involved in the inhibition of thirst.

Animals↗

Melatonin effects on inhibition of thirst and fever induced by lipopolysaccharide in rat.

In 24 h water deprived rats we have evaluated the effects of melatonin on the inhibition of thirst and on fever induced by Escherichia coli lipopolysaccharide. Intraperitoneal (i.p) injection of lipopolysaccharide (0.32, 0.64 and 0.96 mg/kg) alone induced, a dose-dependent and significant inhibition of water intake as well as fever. In addition, lipopolysaccharide at the same concentrations increased urinary prostaglandins and serum cytokines levels. On the contrary, lipopolysaccharide treatment had no effects on cerebral brain nitric oxide synthase activity. All lipopolysaccharide effects were reverted by a prior, concomitant and subsequent i.p. treatment with melatonin (2, 4 and 6 mg/kg), whereas they were still present when melatonin was injected in combination with the melatonin receptor antagonist luzindole (15, 30 and 60 mg/kg, i.p.). We suggest that melatonin could exert its dipsogenic effects through a reduction of the free radical nitric oxide (NO.) whereas it may reduce body temperature by preventing an excessive formation of prostaglandins and cytokines.

Animals↗

Chronic hypernatremia from a congenital defect in osmoregulation of thirst and vasopressin.

An infant with microcephaly and delayed development was found to have chronic asymptomatic hypernatremia. Computerized brain tomography disclosed dysplasia of the midline structures, septum pellucidum and corpus collosum. Evaluation revealed defective osmoregulation, hypothalamic hypothyroidism, and hypogonadotropinism. He showed no desire to drink at plasma osmolalities over 330 mOsm/kg. His plasma vasopressin levels (less than or equal to 1.4 pg/ml) were inappropriately low relative to his high levels of plasma osmolality (greater than or equal to 310 mOsm/kg), which might be accounted for by either deficient neurohypophyseal vasopressin stores or disturbance of the hypothalamic osmoreceptors governing vasopressin. The first possibility was ruled out by demonstrating normal vasopressin response (167 pg/ml) to nonosmotic (emetic) stimulation. Under baseline conditions, his urine was concentrated up to 747 mOsm/kg and urine volume was low. With water loading, maximal water diuresis developed (urine osmolality 68 mOsm/kg), but his plasma osmolality remained in the hyperosmolar range (312 mOsm/kg). Treatment with a vasopressin analogue, desamino-D-arginine vasopressin, and forced hydration restored plasma osmolality and plasma sodium to normal. These findings indicate a severe defect in the hypothalamic osmoreceptors controlling thirst and vasopressin secretion with normal vasopressin stores and preserved vasopressin responsiveness to nonosmotic stimuli. To our knowledge, this report provides the first documentation of selective osmoreceptor defect in conjunction with congenital dysplasia of midline brain structures.

Brain↗

Thirst and vasopressin secretion counteract dehydration in newborn infants.

OBJECTIVE AND STUDY DESIGN: Our goal was to study the water balance in healthy breast-fed infants (n = 139) during their first 5 days, by cross-sectional measurements of body weight, serum sodium, serum osmolality, and hematocrit. We also investigated infants' capacity to conserve body water by increased secretion of vasopressin, the main antidiuretic hormone in human beings. RESULTS: The maximal body weight reduction was 5.7% +/- 1.7% (mean +/- SD) of birth weight and most infants started to gain weight when they were 3 days old. The serum sodium level at 16 +/- 4 hours (on day of birth) was 142 mmol/L; the level increased after 1 day (p < 0.01) and remained constantly high for the following 2 days (p < 0.05). The serum osmolality was increased at 1 day (p < 0.01) and 2 days (p < 0.05) compared with the value on the day of birth (296 mOsm/kg). The plasma vasopressin level was constant up to 24 hours (1 day), but decreased during the next 2 days (p < 0.01). Infants with body weight reduction exceeding 10% (n = 15) had a further elevation of the serum sodium level (p < 0.0001) and serum osmolality (p < 0.0001), and the plasma vasopressin level was twofold higher (p < 0.0001) compared with corresponding levels in infants with less weight reduction. These infants also had a reduced interval between two subsequent feedings (p < 0.001). The hematocrit remained unchanged irrespective of the degree of weight reduction. CONCLUSIONS: When the reduction of body weight exceeds 10%, the newborn infant releases vasopressin in response to fluid hypertonicity. This state also affects feeding behavior, perhaps as an expression of thirst. It is likely that hormone release is also stimulated in parallel with a weight reduction of less than 10%, because it is also accompanied by a hyperosmotic state.

Body Weight↗

Effects of preloads of water and saline on thermal dehydration-induced thirst.

The relative contribution of cellular and extracellular water deficits to the genesis of thirst due to thermal dehydration was studied in male Sprague-Dawley rats following exposure to a 40 degrees C environment for 4 h. Intragastric (I.G.) and intravenous (I.V.) preloads of water reduced the elevated plasma sodium and plasma osmolality of thermally dehydrated rats to control levels, but preloads of saline did not. I.G. and I.V. preloads of saline returned the hematocrit and plasma protein concentration of thermally dehydrated rats to control levels. Both the I.G. water preload and the I.G. saline preload reduced water intake, with the I.G. water preload having a greater effect. The I.V. water preload reduced water intake nearly to control levels, whereas the I.V. saline preload was without effect on water intake. These data indicate that the water intake of thermally dehydrated rats is primarily due to a cellular water deficit and that oral and gastric factors are also important in terminating water intake in thermally dehydrated rats.

Animals↗

Intra- and extracellular dehydration-induced thirst-related behavior in an amphibian.

The behavioral response to dehydration is critical to an animal's survival. Because of their permeable skin, amphibians are particularly sensitive to dehydrating conditions. We tested the hypothesis that different forms of dehydration induce water absorption response (WR) behavior in the desert spadefoot toad, Scaphiopus couchii. First, we determined the behavioral response to intracellular dehydration by treating fully hydrated toads with increasing concentrations of hypertonic solutions of NaCl or sucrose via intraperitoneal injection (i.p.). Animals that were treated to induce intracellular dehydration with either solute exhibited a significant increase in WR behavior compared to vehicle-treated controls. To distinguish that the response was a result of an increased osmotic gradient between the intra- and extracellular compartments, we treated fully hydrated animals i.p. with urea, which freely passes into the intracellular compartment and increases overall animal osmolarity. Urea treatment did not induce WR behavior. To determine the response to extracellular dehydration, the blood volume of fully hydrated toads was reduced via cardiac puncture, and the WR behavior was measured. Animals who had a reduction in blood volume exhibited a significant increase in WR behavior compared to sham-punctured controls. Our results are the first to demonstrate that multiple forms of dehydration can induce thirst-related behavior in amphibians.

Animals↗