Influence of ruminal water‐loading on renal sodium excretion and water intake following feeding in sheep

We investigated the effect of ruminal water loading before feeding on the natriuretic and drinking responses that follow feeding. Six sheep fed 800 g of chaff drank 1360 ± 150 mL during the 5 h immediately following feeding and increased renal Na excretion. Plasma Na concentration increased by 4 mmol L^–1 and plasma osmolality by 9 mosmol kg^–1 within 1.5 h and remained elevated. A rumen load of water administered before feeding prevented the increases in plasma Na and osmolality without affecting feeding. The natriuresis, water drinking and vasopressin secretion in response to feeding were abolished. Total sodium excreted during the experiment was halved in water‐loaded animals compared with untreated animals (30.4 ± 2.1 mmol^–1 cf. 63.8 ± 2.9 mmol^–1; P < 0.01). Ruminal loading with isotonic saline caused a 33% reduction in postprandial drinking, however, reducing cerebrospinal fluid NaCl concentration abolished postprandial drinking and natriuresis. Intravenous infusion of isotonic dextran appeared to delay the onset of water intake without changing the total volume of water drunk, suggesting a role of plasma volume in initiating drinking. We conclude from the data that central osmoregulatory mechanisms that include increased sodium excretion as well as thirst and vasopressin release are activated following food intake by sheep.     

Influence of ruminal water-loading on renal sodium excretion and water intake following feeding in sheep.

We investigated the effect of ruminal water loading before feeding on the natriuretic and drinking responses that follow feeding. Six sheep fed 800 g of chaff drank 1360 +/- 150 mL during the 5 h immediately following feeding and increased renal Na excretion. Plasma Na concentration increased by 4 mmol L (-1) and plasma osmolality by 9 mosmol kg (-1) within 1.5 h and remained elevated. A rumen load of water administered before feeding prevented the increases in plasma Na and osmolality without affecting feeding. The natriuresis, water drinking and vasopressin secretion in response to feeding were abolished. Total sodium excreted during the experiment was halved in water-loaded animals compared with untreated animals (30.4 +/- 2.1 mmol (-1) cf. 63.8 +/- 2.9 mmol-1; P < 0.01). Ruminal loading with isotonic saline caused a 33% reduction in postprandial drinking, however, reducing cerebrospinal fluid NaCl concentration abolished postprandial drinking and natriuresis. Intravenous infusion of isotonic dextran appeared to delay the onset of water intake without changing the total volume of water drunk, suggesting a role of plasma volume in initiating drinking. We conclude from the data that central osmoregulatory mechanisms that include increased sodium excretion as well as thirst and vasopressin release are activated following food intake by sheep.     

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.     

Influence of mannitol-induced reduction in CSF Na on nervous and endocrine mechanisms involved in the control of fluid balance

Infusions (20 μl/min) of isotonic (0.27 M) and hypertonic (0.7 M) mannitol dissolved in Na-free artificial CSF were made for 1 h. into the lateral cerebral ventricle (IVT) of conscious water-replete sheep. The IVT infusion of both 0.27 M and 0.7 M mannitol induced a water-diuresis. Samples of CSF were collected prior to, and 5, 35, 65 and 125 min after the end of the infusion. These consistently showed a reduction in CSF [Na], while CSF osmolality remained unchanged after 0.27 M mannitol, and was considerably increased after 0.7 M mannitol. In the 44 h dehydrated sheep IVT infusion of 0.7 mannitol in Na-free artificial CSF was made for 6 h. The water deprivation as such caused a marked increase in plasma and CSF [Na] and osmolality. The 6 h IVT infusion of hypertonic mannitol further increased the CSF osmolality, while CSF [Na] decreased and reached a value below the normal for water-replete animals. The infusion also induced a fall in plasma ADH resulting in a water-diuresis, and extinguished the thirst of the dehydrated sheep. Furthermore, the infusion markedly reduced renal sodium excretion without causing any substantial change in blood aldosterone, in spite of the fact that there was a conspicuous increase in plasma renin concentration. The study supports the view that sodium sensitive receptors close to the cerebral ventricular system participate in the regulation of ADH secretion, water intake, renin release, and renal sodium excretion.     

Plasma Renin Activity Following Central Infusion of Angiotensin II and Altered CSF Sodium Concentration in the Conscious Goat

To study central influences on the renal release of renin, angiotensin II was infused into the lateral cerebral ventricle of conscious hydrated goats. CSF sodium concentration was increased or lowered by similar infusions of hypertonic NaCl or of isotonic fructose solution. Infusion of anglotensin II in doses from 0.5 to 1 μg caused a drop in plasma renin activity (PRA) and elicited a rise in blood pressure, antidiuresis, natriuresis, and thirst. Intraventricular infusion of hypertonic NaCl also suppressed PRA, induced anti-diuresis, natriuresis, and an inconsistent rise in blood pressure. Lowering of CSF [Na⁺] by infusion of isotonic fructose caused a rise in PRA and was followed by a water diuresis in the non-hydrated animal. The fructose infusions caused some decrease in renal K⁺ excretion but no consistent change in renal Na⁺ excretion. The results indicate that angiotensin II and changes in sodium balance modulate renal renin release also via the central nervous system.     

A central osmosensitive receptor for renal sodium excretion.

1. The effect on renal Na and water excretion of increasing the NaCl concentration of blood supplying the brain was investigated in conscious water-loaded sheep. Intracarotid infusion ot 4 M-NACl at 0-8 ml./min for 60 min was compared with equivalent intrajugular infusion. 2. A more rapid increase in renal Na excretion and urine osmolality occurred with the intracarotid infusions than with intrajugular infusions. 3. Intracarotid infusions of 2 M sucrose or fructose at 1-6 ml./min for greater increase in renal Na excretion, urine osmolality and a decrease in urine flow rate. 4. The results suggest that there are receptors in the brain sensitive to changes in extracellular tonicity which influence renal Na excretion. It is possible that changes in ADH secretion alone mediate the early natriuresis seen with intracarotid hypertonic infusions although an alternative concurrent mechanism cannot be ruled out.     

Renal and hormonal responses to atrial natriuretic peptide infusions in goats on high and low sodium intake

Synthetic atrial natriuretic peptide (ANP) was infused intravenously (1 microgram min-1; 60 min) in five goats during two series of experiments. For at least 4 weeks before the ANP infusions the goats received either no salt supplementation (= low sodium diet), or were given 16 g NaCl mixed with the food each day (Na = 274 mmol day-1; high sodium intake). The goats were changed between the treatments at random. ANP infusions caused diuresis, natriuresis and haemoconcentration during both diets. The urinary Na excretion increased about four-fold during the high sodium intake, and about 10 times during the low sodium intake. The urinary K excretion increased significantly during the low sodium diet, but decreased slightly during the high sodium intake. During both diets the K excretion became significantly lowered after the infusions. The mean glomerular filtration rate (GFR) was generally lower during the low sodium diet, but increased significantly during ANP infusions on both diets. The GFR returned to baseline immediately after the infusions, in contrast to urine flow and urinary Na excretion. Renal free water clearance increased slightly at the end of the infusion during the low sodium diet, but did not change during the high salt diet. Plasma renin activity (PRA) and plasma aldosterone concentration fell during ANP infusions in goats on the low sodium intake, but did not change significantly during the high sodium diet. These results indicate that the diuresis and natriuresis observed during intravenous ANP infusions in goats are mainly due to increased GFR.(ABSTRACT TRUNCATED AT 250 WORDS)     

The dipsogenic effect of intracerebroventricular infusion of hypertonic NaCI 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 NaCI, the water intake in response to 30-min ICV infusons of hypertonic solutions of different Na salts (0.25 M NaCI, Nal, 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/o.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 NaCI in the sheep is mainly caused by the increased Na rather than the CI ion concentration or the hyperosmolality in the extracellular fluid of juxtaventricular brain tissue.     

Isotonic and hypertonic sodium loading in supine humans

The hypothesis that hypertonic saline infusion induces a greater natriuresis than infusion of the same amount of sodium as isotonic saline was tested in 8 supine subjects on fixed sodium intake of 150 mmol NaCl day^–1. Sodium loads equivalent to the amount of sodium contained in 10% of measured extracellular volume were administered intravenously over 90 min either as isotonic saline or as hypertonic saline (850 mmol L^–1). A third series without saline infusion served as time control. Experiments lasted 8 h. Water balance and sodium loads were maintained by replacing the excreted amounts every hour. Plasma sodium concentrations only increased following hypertonic saline infusion (by 2.7 ± 0.3 mmol L^–1). Oncotic pressure decreased significantly more with isotonic saline (4.1 ± 0.3 mmHg) than with hypertonic saline (3.2 ± 0.2 mmHg), indicating that isotonic saline induced a stronger volumetric stimulus. Renal sodium excretion increased more than a factor of four with isotonic and hypertonic saline but also increased during time control (factor of three). Cumulated sodium excretions following isotonic (131 ± 13 mmol) and hypertonic saline (123 ± 10 mmol) were statistically identical exceeding that of time control (81 ± 9 mmol). Plasma angiotensin II decreased in all series but plasma ANP concentrations and urinary excretion rates of endothelin-1 remained unchanged. In conclusion, hypertonic saline did not produce excess natriuresis. However, as the two loading procedures induced similar natriureses during different volumetric stimuli, part of the natriuresis elicited by hypertonic saline could be mediated by stimulation of osmoreceptors involved in renal sodium excretion. The supine position does not provide stable time control conditions with regard to renal excretory function.     

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.     

Renal denervation does not prevent dehydration-induced natriuresis in sheep

Normal sheep or sheep in which the renal nerves had been extirpated were deprived of water for 2 days in order to determine whether changes in renal nerve activity contribute to natriuresis during water deprivation. Both groups of sheep showed a considerable natriuresis throughout the period of water deprivation and increases in plasma osmolality and plasma Na concentration. Renal denervation, as indicated by the absence of catecholamine fluorescence in kidney sections, was extensive. Previous experiments have suggested cerebral involvement in the induction of dehydration-induced natriuresis. The present results indicate that the efferent pathway mediating this cerebral influence on renal sodium excretion does not involve the renal nerves, suggesting a hormonal mechanism as the likely pathway.     

On the importance of CSF Na in the regulation of renal sodium excretion and renin release

Infusions (20 microliters/min) of isotonic (0.27 M) mannitol dissolved in Na-free artificial cerebrospinal fluid (CSF) were made for 2 h into the lateral cerebral ventricle (IVT) of conscious 68 h dehydrated sheep. The IVT infusion induced a conspicuous drop in renal sodium excretion and marked rise in plasma renin concentration (PRC). The antinatriuretic response to the IVT infusion was not altered by the intravenous administration of ADH or te converting enzyme blocker (SQ 14225, Captopril). Surgical bilateral renal denervation did not change the antinatriuretic response while the increase in PRC was extinguished. Samples of CSF were collected prior to, and 15 min after the end of the infusion. These showed a reduction in CSF [Na], while CSF osmolality remained unchanged. The study supports the view that sodium sensitive receptors close to the cerebral ventricular system participate in the regulation of renal sodium excretion and renin release, it also suggests that renal sodium excretion is affected by an unknown hormonal factor of cerebral origin, while the release of renin seen in response to a reduction in CSF [Na] is mediated by the renal nerves.     

An attempt to quantitate the contribution of antidiuretic hormone to the diuresis of left atrial distension in conscious dogs

In order to quantitate the contribution of the antidiuretic hormone (ADH) to the diuresis of left atrial distension 52 experiments have been performed in 12 conscious, chronically instrumented beagle dogs. Left atrial pressure was increased by a reversible mitral stenosis by about 10 cm H₂O (1.0 kPa) for 60 min. Plasma ADH concentration (range between 1.3 and 6.0 pg·ml^?1) (radioimmunoassay) decreased in every experiment, the average decrease being about 50%. An i. v. infusion of vasopressin (0.05 mU ·min^?1·kg^?1) abolished the diuretic effect of left atrial distension or decreased the urine volume below control values; natriuresis was not affected. The magnitude of the vasopressin effect was dependent on the concurrent sodium excretion: when sodium excretion was low during left atrial distension, vasopressin was more effective in reducing the urine volume than when sodium excretion was high. It is concluded that the diuresis of left atrial distension is mediated (a) by a suppression of ADH and (b) by factors controlling sodium excretion, the contribution of these two mechanisms being dependent on the concurrent sodium excretion.     

Dependency of renal potassium excretion on Na,K-ATPase transport rate

Potassium secretion may depend on the transport rate of Na, K-ATPase in basolateral cell membranes of distal tubular cells. To examine this hypothesis experiments were performed in anaesthetized dogs during inhibition of proximal potassium reabsorption by acetazolamide or mannitol (fractional potassium excretion 1.2-1.4) or additional stimulation of potassium secretion by ethacrynic acid (fractional potassium excretion 2.1). Ouabain in a dose which inhibits 70–80% of the Na, K-ATPase activity reduced fractional potassium excretion to 0.8-0.9 by an effect on distal tubular secretion since potassium transport in the proximal tubules was not affected. Ouabain-sensitive potassium excretion varied in proportion to ouabain-sensitive sodium reabsorption during variation in glomerular nitration rate, even at urinary sodium concentrations exceeding 80 mmol 1^-1. In experiments without ouabain, saline infusion raised potassium excretion and sodium reabsorption until maximal Na, K-ATPase transport rate was reached, as judged from heat production measurements, but not during further increments in urine flow. After inhibition of Na, K-ATPase activity by hypokalaemia, potassium excretion and cortical heat production remained constant over a wide range of urine flow and sodium excretion. We conclude that potassium secretion is dependent on intact Na, K-ATPase activity and is stimulated by sodium delivery to the distal nephron until maximal transport rate of the enzyme is reached.     

Hypothalamic temperature and osmoregulation in the Pekin duck

The temperature of the anterior and middle hypothalamus of conscious Pekin ducks was altered with chronically implanted thermodes. Both urine formation and salt secretion by the supraorbital glands were influenced by hypothalamic cooling. When osmotic diuresis was induced by continuous intravenous infusion of 1.2 ml·min^–1 of 293 mosm·kg^–1 mannitol in H₂O solution, hypothalamic cooling increased urine flow rate at reduced urine osmolality and unchanged osmolal excretion rate. The degree of this cold induced diuresis increased with cooling intensity. Additional ADH administration by continuous infusion at a supramaximal dose abolished the diuretic effect of hypothalamic cooling. When water diuresis was induced by intragastric continuous infusion of 1.2 ml·min^–1 of distilled water, hypothalamic cooling enhanced the diuresis, but hypothalamic warming had equivocal effects. The diuretic effects of hypothalamic cooling suggest an inhibition of endogeneous ADH release by lowering hypothalamic temperature. When the salt glands of salt adapted ducks were stimulated by continuous intravenous infusion of 0.2 ml·min^–1 of 800 mosm·kg^–1 NaCl in H₂O solution, hypothalamic cooling reduced the salt gland secretion rate to an extent depending on cooling intensity. It is concluded that the activities of those integrative and/or efferent hypothalamic neurons, which mediate the hormonal control of renal water absorption and the nervous control of salt secretion by the supraorbital gland, depend on their own temperature.Supported by Deutsche Forschungsgemeinschaft (Si 230/1)     

Canjoint Action of Sodium and Angiotensin on Brain Mechanisms Controlling Water and Salt Balances

Andersson , B. and L. Eriksson , Conjoint action of sodium and angiotensin on brain mechanisms controlling water and salt balances. Acta physiol. scand. 1971. 81. 18–29. The effects on water and salt balances of a simultaneous infusion of angiotensin and hypertonic NaCl into the 3rd brain ventricle were studied in goats in normal water balance and in hydrated animals. For comparison similar infusions of angiotensin alone (solved in slightly hypotonic saline) and of hypertonic NaCl were made. Like the hypertonic NaCl, 30 min infusions of angiotensin alone induced drinking in animals in normal water balance, and an inhibition of the water diuresis in the hydrated goat. The simultaneous infusion of both substances resulted in a marked potentiation of the dipsogenic and the antidiuretic effects. A possible explanation may be that angiotensin facilitates the transport of Na⁺ into brain cells regulating thirst and ADH release, and that the intracellular Na⁺ concentration rather than strictly osmotic factors determines the activity of these cells. In the hydrated goat a central effect of angiotensin strongly enhanced the natriuretic response to intraventricular infusions of hypertonic NaCl, and extreme natriuresis developed as result of the combined infusions in hydrated, salt-supplemented animals. During normal water balance this sodium-angiotensin synergism was less obvious, which suggests that both an expanded fluid volume and an elevated intracellular Na⁺ concentration are needed for optimal activation of a brain mechanism which stimulates renal Na' excretion, The time course of the centrally induced natriuresis indicates that the effect on the kidney may be mediated by a humoral agent.     

Natriuresis obtained by intracerebroventricular infusion of hypertonic NaCI in rats with papillary necrosis.

Raising the sodium concentration in the third cerebral ventricle increases renal sodium, potassium and water excretion. The identification and characterization of the factor(s) mediating the centrally evoked natriuresis would be greatly facilitated if the exact intrarenal effector site were known. We have assessed the importance of inner medullary structures for the effects of CNS stimulation by examining its ability to alter renal excretion in rats with papillary necrosis, induced 2 d earlier with 2-bromoethylamine hydrobromide (BEA), 250 mg kg^-1 body wt i. v. Male Lewis x DA rats were divided into a BEA-treated group (n = 6) and a control group receiving vehicle alone (n = 6). In contrast to the white papillae normally seen, the papillae of BEA-treated animals were bright red and showed a clear line of demarcation at their base. The rats were anaesthetized i. p. with Inactin (120 mg kg^-l body wt). Artificial cerebrospinal fluid (CSF) was infused (520 nL min^-1) via a cannula into the left lateral ventricle. After 45 min CSF containing 1 M NaCl was used. Stimulation of the control rats with hypertonic CSF increased urine flow rate five-fold (5.4± 0.8 to 27.1±6.1 μL min^-1), Na excretion 23-fold (0.4±0.1 to 7.6±1.8 μmol min^-1) and K excretion fourfold (0.6±0.18 to 3.8±O.5 pmol min^-1). When the concentration mechanisms were damaged with BEA, the basal excretion rates of water and Na increased. The natriuretic response to ICV stimulation was severely impaired in these rats, but the kaliuretic effect was sustained. In conclusion, the natriuretic effect of ICV stimulation with hypertonic CSF is dependent on an intact renal inner medulla, which is not the case for the less pronounced kaliuretic response. Thus, either the juxtamedullary nephrons possess marked natriuretic responsiveness, not present in the cortical ones, or the responsiveness lies mainly in the papillary collecting ducts. However, it cannot be excluded that a disturbance of salt balance contributes to the observations.     

Change of tubular reabsorption of sodium and water after denervation

1. Renal function was compared in dogs before and after denervation, with normal or reduced glomerular filtration rate (GFR). GFR was reduced by one of two means, aortic clamping or injection of plastic microspheres into one renal artery.

2. The data showed that the tubular rejection fraction of denervated kidneys increased at a time when the same value for the control kidney decreased, indicating that denervation diuresis is not simply a result of increased filtered load of Na and water.

3. Changes in excretion after aortic clamping are not due solely to reduced filtered load. A reduction in renal blood pressure itself appears to have a direct effect on Na transport since Na excretion was significantly decreased before there were any changes in GFR, renal plasma flow and urine volume.

4. When GFR in a denervated kidney was reduced by microsphere injection it was demonstrated that a significant natriuresis (U_Na V) and diuresis (V) occurred when. GFR was reduced by as much as 40%.

5. These experiments support the hypothesis that denervation diuresis does not result solely from increased filtered load, but entails altered Na transport.

     

Renal sodium excretion after oral or intravenous sodium loading in sodium-deprived normotensive and spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats that had been on a low sodium diet for 3 days were given 1.5 mmol sodium chloride kg^-1 body weight either orally or intravenously. The rats receiving an oral sodium load showed a greater natriuresis than those receiving the same saline load intravenously. No increase of renal sodium excretion was observed when the rats received a hypertonic mannitol solution orally. The cumulative sodium excretion during the 8 h following oral loading was two to three times larger in SHR than in WKY, whereas no difference between strains could be demonstrated after giving saline intravenously. Furthermore, after switching from normal to low sodium diet the rate of decrease of renal sodium excretion was greater in SHR than in WKY rats. It is proposed that there exists a gastrointestinal sensory mechanism for sodium controlling the renal sodium excretion. Furthermore, it is suggested that the function of this mechanism differs between SHR and WKY.     

Effects of 1-deamino-1-monocarb-arginine-vasotocin on sodium ion and water excretion by rat kidneys

Injection of 1-deamino-1-monocarb-arginine-vasotocin (0.05 μg/100 g body weight) to alert rats caused increased natriuresis, diuresis, and reabsorption of osmotically free water. Injection of furosemide (0.5 mg/100 g body weight) increased Na⁺ excretion and did not increase reabsorption of osmotically free water. 1-Deamino-1-monocarb-arginine-vasotocin in molar conversion increased natriuresis by almost 6×10⁴ times more effectively than furosemide. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 5, pp. 494–497, May, 2007