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.     

Role of angiotensin-II in the polydipsia of diabetes insipidus in the Brattleboro rat

Captopril, an inhibitor of angiotensin converting enzyme which prevents conversion of angiotensin I (AI) to angiotensin II (AII), reduces the polydipsia of Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI). In the present study, captopril (480 mg/kg-day) reduced DI polydipsia by 18% with no change in plasma osmolality; an equivalent (17%) reduction caused by quinine (0.02%) adulteration of drinking water increased plasma osmolality significantly. If captopril reduces water intake of DI rats because it removes a dipsogenic signal to the CNS, plasma osmolality should have increased during captopril treatment. Captopril probably reduces DI polydipsia because it reduces renal water loss by lowering blood pressure. Both furosemide and spironolactone, which reduce renal water loss and increase AII levels, also reduced DI polydipsia with no change in plasma osmolality. Thus, only a small fraction of DI polydipsia seems to be controlled by a dipsogenic effect of AII.     

Evidence for an influence of CSF sodium concentration upon ACTH-mediated cortisol response to intravenous and intracerebroventricular angiotensin II

The influence of cerebrospinal fluid (CSF) NaCl concentration upon the cortisol release induced by intracerebroventricular (i.c.v.) and intravenous (i.v.) infusions of angiotensin II (AII) was studied in conscious goats. A first series of experiments involved i.c.v. infusion (20 min; 20 microliters min-1) of simply hypertonic (0.5 M) NaCl, or of AII (2 pmol kg-1 min-1) dissolved in 0.5 M or isotonic (0.15 M) NaCl or in isotonic glucose. The most pronounced rise in plasma cortisol concentration (PC) was elicited by AII in 0.5 M NaCl, but responses of nearly the same size were obtained by merely 0.5 M NaCl and by AII in isotonic NaCl, whereas AII in glucose induced a smaller PC rise. An urge to drink developed during all infusions, except during the AII/glucose infusion. Here, however, thirst became apparent 2-6 min post-infusion. When, in a second series, the hypertonicity of the NaCl was reduced to 0.3 M, and the dose of AII to 0.5 pmol kg-1 min-1, only the infusion of AII in 0.3 M NaCl elicited any appreciable rise in PC. The response was approximately the same size as that earlier obtained as the effect of the larger dose of AII dissolved in isotonic saline. In a third series of experiments, a 30-min i.c.v. infusion of isotonic glucose, preceding and out-lasting a 10-min i.v. infusion of AII (40 pmol kg-1 min-1), was found to extinguish the rise in PC obtained as the effect of a separate i.v. infusion of AII.(ABSTRACT TRUNCATED AT 250 WORDS)     

Water drinking caused by intracerebroventricular infusions of hypertonic solutions in cattle

Infusions into the lateral cerebral ventricle of hypertonic solutions of NaCl, mannitol or sucrose all induced water drinking in cattle. However, infusion of hypertonic NaCl caused a significantly greater water drinking response than did the infusions of mannitol or sucrose, despite the fact that CSF osmolality increase was similar. In contrast, hypertonic solutions of NaCl or mannitol had similar dipsogenic effects when infused intravenously. The intracerebroventricular infusions of hypertonic NaCl or mannitol did not affect the intakes of food or Na solution. The results are consistent with the hypothesis that both cerebral osmoreceptors and Na sensors are involved in regulating thirst in cows.     

Effect of intracerebroventricular deuterium oxide on water intake and AVP release induced by intravenous infusion of angiotensin II in sheep

The effect of intracerebroventricular (i.c.v.) infusion (0.02 ml min-1) of deuterium oxide (D2O), with NaCl added to isotonicity, on the water intake and arginine vasopressin (AVP) release caused by intravenous (i.v.) infusion of angiotensin II (AII) (4.8 nmol min-1) was studied in euhydrated sheep. The i.c.v. infusion of D2O, which started 80 min before commencement of the AII infusion, induced a water diuresis in four out of six animals and a measurable decrease in plasma AVP concentration. The i.v. infusion of AII effectively stimulated the AVP release and the response was unaffected by prior and simultaneous i.c.v. administration of D2O. However, the water intake measured 2 min after cessation of the AII administration was reduced by 50% when D2O was infused i.c.v. compared to that seen after simply the AII infusion. The inhibitory effect of D2O on AII-induced drinking disappeared rapidly after discontinuation of D2O administration. Compensatory increased drinking was seen during the first post-infusion hour, resulting in an equivalent cumulative intake of water at 60 min post-infusion in the two types of experiments. The present results support the idea that at least some of the cerebral effects of circulating AII on fluid balance are medicated via targets which are simultaneously accessible to influences from the blood and the cerebrospinal fluid.     

Comparison of the effects of the dipeptidyl peptidase inhibitors captopril, ramipril, and enalapril on water intake and sodium appetite of Sprague-Dawley rats

Two experiments were performed with Sprague-Dawley rats to study the effects of different inhibitors of angiotensin I converting enzyme (ACE) on water intake and sodium appetite. Subcutaneous administration of low doses of either enalapril (MK421) or ramipril (Hoe498), like captopril, was dipsogenic. Acute administration of ramipril also enhanced the drinking response to peripherally administered angiotensin I (Ang I). Higher doses inhibited the drinking response to Ang I, administered acutely either peripherally or centrally. These data provide behavioral evidence that the nonsulfhydryl inhibitors enalapril and ramipril inhibit brain converting enzyme activity and that they are considerably more potent than captopril. All three of these compounds, administered chronically in food, induced an appetite for sodium chloride (NaCl) solution. Enalapril and ramipril were more potent than captopril. Plasma renin activity was increased by each of these inhibitors, but the magnitude of the increase was not clearly related to the amount of NaCl consumed. The water intake in response to acute administration of either Ang I or isoproterenol was not reliably increased in rats treated chronically with these inhibitors.     

The dipsogenic effect of intracerebroventricular infusion of hypertonic NaCl in the sheep is mediated mainly by the Na ion

In order to examine the importance of the chloride ion in the dipsogenic effect of intracerebroventricular (ICV) infusion of hypertonic NaCl, the water intake in response to 30-min ICV infusions of hypertonic solutions of different Na salts (0.25 M NaCl, NaI, NaSCN and 0.125 M Na2S2O3), mannitol (0.5 M) and choline chloride (0.25 M) was studied in the sheep. All solutions of the Na salts caused significant water drinking compared with ICV control infusions of isotonic artificial cerebrospinal fluid (CSF), except Na thiosulphate (Na2S2O3), which was much less effective, even after equilibration of its osmolality with the other sodium solutions by adding mannitol (0.125 M Na2S2O3/0.25 M mannitol). An inconsistent and small intake of water was induced by ICV hypertonic mannitol and choline chloride. It is concluded that the dipsogenic effect of ICV infusion of hypertonic NaCl in the sheep is mainly caused by the increased Na rather than the Cl ion concentration or the hyperosmolality in the extracellular fluid of juxtaventricular brain tissue.     

Operant drinking in pigs following intracerebroventricular injections of hypertonic solutions and angiotensin II

The effect on operant drinking of intracerebroventricular injections of the following solutions has been investigated; hypertonic saline, hypertonic sugars, angiotensin II (Ang II) dissolved in water or dextrose, and Ang II dissolved in saline. Hypertonic (0.85 M) NaCl caused drinking in all pigs tested, but hypertonic (1.7 M) xylose, glucose or sucrose were less effective, indicating involvement of a cerebrospinal fluid sodium receptor mechanism as well as an osmoreceptor mechanism in the drinking responses. Angiotensin II in 0.15 M NaCl caused drinking in all pigs but when dissolved in water or dextrose it was ineffective. Injection of Ang II with hypertonic NaCl produced drinking similar in volume to the sum of the amount drunk in response to the individual stimuli. These results indicate that, in the pig, drinking in response to Ang II requires the presence of sodium ions.     

Dipsogenic Effects of Intracarotid Infusions of Various Hyperosmolal Solutions

Thirst in response to intracarotid and intravenous infusions (1.5 ml/min) of various hypertonic, equi-osmolal solutions was studied in the goat. Intracarotid infusions of 1 M NaCl and of 2 M fructose induced conspicuous cumulative drinking. The amount of water drunk during intracarotid infusions of 2 M urea and glycerol was only about a third of that consumed during the corresponding infusions of NaCl and fructose. During intracarotid infusions of 2 M galactose and glucose drinking was inconsistent. Of the intravenous infusions only hypertonic NaCl had a consistent dipsogenic effect. However, the amount of water consumed was considerably smaller and the latency time for drinking much longer than during the intracarotid infusions of NaCI. It is concluded that intracarotid infusions of hypertonic solutions act as considerably stronger thirst stimuli than corresponding intravenous infusions, and that the most pronounced dipsogenic effect is obtained by intracarotid infusions of those hypertonic solutions which also most effectively release antidiuretic hormone in the hydrated goat. The possibility is discussed that intracarotid infusions may stimulate the thirst mechanism indirectly via a rise in the Na+ concentration of the cerebrospinal fluid.     

The influence of central infusions on drinking due to peripheral osmotic stimuli in the pigeon (Columba livia)

The drinking responses of pigeons infused simultaneously IV (0.334 ml/min) and ICV (2 microliters/min) for 15 min with various osmotic solutions were observed during, and for 60 min after, the combined infusions. Drinking in response to IV infusion of 0.5 M NaCl or 1.0 M sucrose was unaffected by simultaneous ICV infusion of 0.15 M NaCl, enhanced by ICV 0.3 M NaCl, inhibited during the infusion of water ICV and attenuated by ICV infusion of 0.9 M sucrose. Drinking in response to IV infusion of 1.0 M NaCl or 1.5 M sucrose, two solutions that would have greatly increased CSF sodium concentration, was only slightly affected by simultaneous ICV infusions of NaCl, sucrose or water. These results show that drinking following IV administration of osmotic stimuli can be affected by ICV infusions that may have further increased or decreased CSF sodium concentration thereby suggesting that CSF sodium concentration may play a "permissive role" in osmotically induced drinking.     

Effect of variation of the composition of CSF in the rat upon drinking of water and hypertonic NaCl solutions

Infusing conscious unrestrained rats with either 0.5 M NaCl-CSF or 0.7 M sucrose-CSF into the lateral cerebral ventricle (IVT) at 38 microliters/hr for 4 hr induced drinking. Although the infusates were nearly equiosmotic, water drinking during the 0.5 M NaCl-CSF was greater than during 0.7 M sucrose-CSF. However, IVT infusions of 0.7 M mannitol-CSF at rates of 9.4 microliters/hr or 38 microliters/hr for 4 hr or 10 microliters/hr for 4 days failed to induce water drinking. Also, IVT infusion of 0.27 M mannitol-CSF at 38 microliters/hr for 4 hr failed to significantly alter water drinking. CSF [Na] was reduced by IVT infusion of either 0.7 M sucrose-CSF or 0.7 M mannitol-CSF. In contrast, CSF [Na] was increased by 4-hr IVT infusion of 0.5 M NaCl in rats denied access to water during the infusion. Intake of 0.5 M NaCl was not altered significantly from control intakes by any of the above IVT infusions. It is concluded that water drinking in the rat may be initiated by stimulation of either a sodium sensitive sensor alone or with an osmoreceptor system and that species specific differences in the induction of both water drinking and hypertonic saline drinking are apparent.     

Central AT1 and AT2 receptors mediate chronic intracerebroventricular angiotensin II-induced drinking in rats fed high sodium chloride diet from weaning

Intracerebroventricular (ICV) angiotensin (AIl) administration stimulates central AII receptors to induce water consumption in rats. The aim of this study was to determine the role of brain AT1 and AT2 receptors in mediating chronic ICV AII-induced drinking in rats raised on normal or high sodium chloride diets from weaning. Rats were weaned at 21 days of age and placed on normal or high sodium chloride diet for 10-12 weeks. At adulthood, the animals were instrumented with brain lateral ventricular cannulas and femoral arterial catheters. Low dose chronic central AII infusion (20 ng min(-1)) significantly (P < 0.05) increased water intake in both groups of rats when compared with their respective controls of 24 h artificial cerebrospinal fluid infusions. In a separate group of high sodium fed rats, coinfusion of AII with the AT1 receptor antagonist, losartan (0.25 microg min(-1)) or the AT2 receptor blocker, PD 123319 (0.50 microg min(-1)) blocked chronic ICV AII-induced drinking. Upon reinfusion of AII water intake increased above control. Following the cessation of AII infusions, water intake returned to values not significantly different from control (P > 0.05). In contrast, in the normal sodium fed rats losartan, but not PD 123319, blocked the AII-mediated water intake. The data demonstrate that in high sodium chloride fed rats AII stimulates both central AT1 and AT2 receptors to induce drinking, while in the normal sodium chloride fed rats the peptide activates the drinking response primarily by stimulation of central AT1 receptors.     

Water intake and changes in plasma and CSF composition in response to acute administration of hypertonic NaCl and water deprivation in sheep

Water intake and changes in plasma and cerebrospinal fluid (CSF) composition were measured in response to intracerebroventricular (i.c.v.) and intracarotid infusions of hypertonic NaCl solutions and after 48 h of water deprivation in sheep. Significant interindividual differences in dipsogenic sensitivity to i.c.v. NaCl were found, whereas no such differences were observed in response to intracarotid infusion of hypertonic NaCl. In the more sensitive animals, the increase in CSF [Na] at initiation of drinking during i.c.v. infusion did not differ significantly from the increase in plasma [Na] seen at the thirst threshold during intracarotid infusion of 1 M NaCl. The thirst-eliciting infusions of hypertonic NaCl into the carotid arteries were associated with a small, significant, increase in CSF [Na], which however did not differ from that caused by an i.c.v. non-dipsogenic 'control' infusion of a slightly hypertonic (0.154 M) NaCl solution. Water deprivation for 48 h induced increases in CSF and plasma [Na] similar to those observed at the onset of drinking in response to i.c.v. and intracarotid infusions of hypertonic NaCl. However, the dehydrated animals drank about four times the amount of water consumed in response to the separate treatments with hypertonic NaCl. It is concluded that significant interindividual differences in dipsogenic sensitivity to osmotic stimuli are present in sheep, and that these differences may not necessarily be simultaneously expressed on both sides of the blood-brain barrier. The thirst-eliciting effect of intravascular infusion of hypertonic NaCl may be induced without concomitant increase in CSF [Na] and/or osmolality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lowered cerebrospinal fluid sodium antagonizes effect of raised blood sodium on salt appetite

Moderately Na-deficient sheep (i.e., Na deficit = 300-400 mmol) will correct their deficit when given hypertonic NaHCO3 solution to drink. Access to NaHCO3 was provided by bar press for 2 h only each day following 22 h of salivary loss from a parotid fistula. Each delivery by bar press provided 9 mmol of NaHCO3 and, of the 46.3 +/- 2.5 deliveries made and drunk in 2 h, 80-90% were made in the first 20 min. Ten minutes before access to NaHCO3 commenced an intracarotid infusion of 4 M NaCl at 1.6 ml/min for 30 min was initiated. This infusion reduced intake by approximately 80% and increased both plasma and cerebrospinal fluid sodium concentration (CSF[Na]). Intraventricular (ivt) infusion of 0.7 M mannitol in artificial CSF at 1 ml/h for 3 h begun 1 h before access to Na by bar press lowered CSF[Na] and approximately doubled voluntary Na intake. The combination of the two procedures resulted in NaHCO3 intake similar to base line. That is, the ivt infusion of 0.7 M mannitol counteracted the inhibition of Na appetite produced by the systemic infusion of hypertonic NaCl, and this was associated with attenuation of the effect of the systemic 4 M NaCl infusion on CSF[Na]. The results suggest that the effects of both the ivt and the systemic infusions are mediated via the same sensor system located within the neuropil.     

Analysis of reabsorbate concentrations in the proximal tubules of dog kidneys during osmotic diuresis

To examine to what extent the reabsorbate concentrations, calculated as the flux ratios between solutes and water, represent the fluid composition in the lateral intercellular space (LIS) in the proximal tubules, reabsorption was stimulated by elevating PCO2 from 5 to 13 kPa before and during infusion of mannitol to a plasma concentration of 70 mM in volume-expanded dogs receiving ethacrynic acid. The reabsorbate concentration of NaHCO3 increased by 50 mM during mannitol infusion. The real concentration of NaHCO3 in LIS could not, however, be elevated by this amount, since the driving forces for fluid reabsorption then would have increased during osmotic diuresis due to diffusion of mannitol into LIS from plasma. A model analysis of diffusion in LIS showed that transcellular transport can only lead to trivial increases of LIS concentrations compared to plasma, whereas diffusion across tight junctions can increase LIS concentrations by several mM. NaCl diffusion and coupled transcellular water transport may therefore represent a significant contribution to total bicarbonate-dependent NaCl and water reabsorption in the proximal tubules.     

Effect of angiotensin II on renal water excretion.

In the present study the effect of angiotensin II (AII) on renal water excretion was evaluated. In dogs undergoing a water diuresis, neither the intravenous (IV) (40ng/kg per min) nor intracarotid (5-10 ng/kg per min) infusion of AII significantly altered urinary osmolality (Uosm) or free-water clearance (CH2O). Intravenous infusion of a competitive inhibitor of AII (1-sarcosine,8-glycine AII) into hydropenic dogs also failed to alter Uosm and CH2O significantly. To examine whether AII might suppress, rather than stimulate, vasopressin release, AII was also infused into hydropenic animals. No effect on Uosm and CH2O was observed during the intracarotid infusion. A significant fall in Uosm and rise in CH2O occurred during the intravenous AII infusion, but reversal after cessation of the infusion was incomplete and statistically not significant. Some suppression of antidiuretic hormone (ADH) release during the intravenous infusion of AII, however, was suggested since no similar alteration in renal water excretion was observed during an intravenous AII infusion in hypophysectomized animals receiving a constant infusion of ADH. Taken together, the present results provide no evidence for a direct effect of AII to alter ADH release or to interfere with the peripheral action of ADH. Suppression of ADH release may sometimes occur with pressor doses of intravenous angiotensin, but this effect is clearly less consistent than previously observed with intravenous norepinephrine.     

Central AT1 and AT2 receptors mediate chronic intracerebroventricular angiotensin II‐induced drinking in rats fed high sodium chloride diet from weaning

Intracerebroventricular (ICV) angiotensin (AIl) administration stimulates central AII receptors to induce water consumption in rats. The aim of this study was to determine the role of brain AT₁ and AT₂ receptors in mediating chronic ICV AII‐induced drinking in rats raised on normal or high sodium chloride diets from weaning. Rats were weaned at 21 days of age and placed on normal or high sodium chloride diet for 10–12 weeks. At adulthood, the animals were instrumented with brain lateral ventricular cannulas and femoral arterial catheters. Low dose chronic central AII infusion (20 ng min^?1) significantly (P < 0.05) increased water intake in both groups of rats when compared with their respective controls of 24 h artificial cerebrospinal fluid infusions. In a separate group of high sodium fed rats, coinfusion of AII with the AT₁ receptor antagonist, losartan (0.25 μg min^?1) or the AT₂ receptor blocker, PD 123319 (0.50 μg min^?1) blocked chronic ICV AII‐induced drinking. Upon reinfusion of AII water intake increased above control. Following the cessation of AII infusions, water intake returned to values not significantly different from control (P > 0.05). In contrast, in the normal sodium fed rats losartan, but not PD 123319, blocked the AII‐mediated water intake. The data demonstrate that in high sodium chloride fed rats AII stimulates both central AT₁ and AT₂ receptors to induce drinking, while in the normal sodium chloride fed rats the peptide activates the drinking response primarily by stimulation of central AT₁ receptors.     

Oro-gastro-intestinal inhibition of hypernatremia-induced drinking in the goat

Reduction of drinking by slow (5 ml/min) administration for 20 min of nearly body-warm (35°C) and cold (15°C) water into the mouth, the abomasum, or the duodenal bulb was studied in goats made thirsty by the simultaneous i. v. infusion of hypertonic (2 M) NaCl at 2 ml/min. During the control experiments the drinking response to corresponding infusion of 1.7 M NaCl was recorded. This in order to eliminate the possible influence on the results of a postabsorptive thirst inhibition which would occur if the administered water was completely absorbed already during the saline infusion. The entrance of warm water into the mouth or into the abomasum caused about 20%, and into the duodenal bulb about 30% reduction of drinking during the infusion of hypertonic NaCl. The corresponding reduction for cold water was when introduced into the mouth and duodenal bulb about 50% and into the abomasum about 60%. Cold water also considerably delayed the onset of dringing. The inhibition obtained during cold water administration was partially compensated for by increased post-infusional dringing. As regards the sensory input underlying preabsorptive inhibition of thirst, it is concluded that (regardless of distension, swallowing, and other mechanical factors) the entrance of pure water into various parts of the alimentary tract contributes to reduce the thirst drive. In addition, stimulation of oral, gastric, and duodenal cold receptors obviously diminish the urge to drink considerably.     

Postnatal development of the renin-angiotensin system in rats

The purpose of this investigation was to correlate the development of the various enzyme activities associated with the renin-angiotensin system with age-related differences in the steady-state concentrations of angiotensin I (AI) and II (AII). Angiotensin was quantified by radioimmunoassay. Plasma renin activity and concentration increased between birth and 3 wk of age, and declined thereafter to adult values. Renal renin content, on the other hand, increased throughout the first 6 wk of postnatal life. The concentration of AII in plasma also increased following birth; however, maximum concentrations were not attained until 5 wk of age. In contrast, plasma AI did not increase between 3 and 6 wk of age. These data suggest that the steady-state concentration of AII in neonatal rat plasma may be partially limited by the low plasma renin substrate concentration. The increase in AII between 3 and 6 wk of age may reflect the increasing converting enzyme activity.     

Effects of exogenous angiotensin II in the Atlantic cod,Gadus morhua Observations on gastric acid secretion,gastric sham drinking,and gastric mucosal plasma flow (14C-aniline clearance)

Cods were equipped with cannulae for drainage of the stomach and for the separate perfusion of the stomach (pure seawater containing phenol red as a volume marker) and intestine (diluted seawater). Acidity of the gastric effluence was titrated, its volume calculated from the phenol red concentration. Gastric mucosal plasma flow (MPF) was estimated by gastric ¹⁴C-aniline clearance, I.m. injection of angiotensin II (AII) depressed basal acid secretion in a dose-dependent fashion. Also the MPF was reduced, but relatively less than the secretory depression. Therefore, the AII-induced secretory inhibition could not be explained by restrained mucosal blood flow. Perfusion of the intestine with diluted seawater, or a continuous i.m. infusion of 0.6% NaCl both rendered the fishes non-drinking. A high dose of All (150 μg/kg·h) induced drinking in intestinally perfused cod while lower doses (15, 50 μg/kg·h) did not. In i.m. saline-injected cod, all three doses were dipsogenic. The results suggest that 0.6% saline infusion induces a permanent satiety and that intestinal perfusion in addition induces a preabsorptive satiety. The preabsorptive satiety appears more resistant to the dipsogenic action of AII than the permanent one.