Solute-free Water Reabsorption Research Articles

THE EFFECT OF INTRAVENOUS HYPERTONIC SALINE INFUSION ON RENAL FUNCTION AND VASOPRESSIN EXCRETION IN SHEEP

Conscious Merino ewes were given an intravenous hypertonic sodium chloride load of 4 mmol.min-1 for 100 min. This resulted in increases in urine flow, sodium and potassium excretion and plasma sodium concentration and osmolality. Urinary vasopressin output and solute-free water reabsorption increased and plasma renin activity declined. Renal plasma flow and glomerular filtration rate (GFR) rose, as did the solute clearance. The change in urinary osmolality was related to the initial urine osmolality such that when the initial urine osmolality was high the urine became more dilute, and vice versa. Tubular sodium reabsorption increased but the fractional reabsorption rate fell. It is suggested that the increase in GFR was at least partly due to the increase in AVP and that the electrolyte loss can be accounted for by the increase in GFR without necessarily involving AVP or other hormonal effects at the tubular level.

THE EFFECTS OF TWO ANALOGUES OF ARGININE‐VASOPRESSIN (ORNITHINE‐VASOPRESSIN AND DESAMINO‐D‐ARGININE‐VASOPRESSIN) ON KIDNEY FUNCTION IN SHEEP

The effects of intravenous infusion of ornithine-vasopressin (OVP) and desamino-D-arginine-vasopressin (dDAVP) were studied in normal and hydrated Merino sheep. In normal sheep, OVP resulted in a diuresis, increased urinary sodium and potassium excretion, and a fall in the plasma potassium concentration. Renal plasma flow remained constant but glomerular filtration rate and filtration fraction rose markedly. dDAVP in normal sheep was antidiuretic, but its only significant effect was a small decrease in plasma osmolality. In the hydrated sheep OVP was antidiuretic and resulted in increased urinary excretion of sodium and potassium, and a fall in the plasma potassium level. Renal plasma flow fell, but glomerular filtration and filtration fraction tended to rise. dDAVP in the hydrated sheep was also antidiuretic but urinary sodium and potassium excretion was reduced. Renal plasma flow and glomerular filtration fell, with a small decrease in filtration fraction. These results suggest that the diuretic effect in normal sheep and the electrolyte-excreting effects in both normal and hydrated sheep of OVP are related to the increase in glomerular filtration, which in turn is dependent on the vasopressor activity of the hormone. The increase in glomerular filtration caused by OVP is due to an increase in the filtration fraction of an unchanged renal plasma flow, which could be brought about by an increase in renal efferent arteriolar tone. The effects of hydration of the sheep were the conventional increased urine flow, decreased urine osmolality and decreased solute-free water reabsorption. Sodium and potassium excretion rose slightly and plasma osmolality fell. Renal plasma flow and glomerular filtration both increased with little change in filtration fraction. These effects could be brought about by suppression of endogenous vasopressin and a decrease in both afferent and efferent renal arteriolar tone.

The effect of high rates of vasopressin administration on renal potassium and sodium excretion during potassium loading in the sheep.

1 The influence of potassium loading on the renal excretion of sodium, potassium and solute during high rate vasopressin administration has been investigated in sheep. 2 Adrenalectomized sheep were infused with 0.43 M KCl at 2 ml/min for 2-2.5 hours. Coincident with the rise in plasma potassium concentration, the urinary excretion of sodium, potassium, solute and water was increased as was the reabsorption of solute-free water. The rates of urinary excretion of sodium and potassium, osmolal clearance (COsm) and solute-free water reabsorption (TcH2O) for the first 50 min of potassium infusion were each found to be linearly related to the plasma potassium concentration. 3 After 50 min an infusion of vasopressin at 1 or 4 mu/min was superimposed on the potassium infusion for a period of 30 minutes. The administration of vasopressin was consistently associated with further augmentation of potassium excretion and clearance, of osmolal clearance and of solute-free water reabsorption to values above those anticipated from the pre-vasopressin regression lines for these parameters. Urinary sodium showed a coincident depression in the rate of excretion and clearance during the same period. 4 Thirty to fifty minutes after the cessation of vasopressin infusion the potassium and sodium excretions had returnied to values which approximated the pre-vasopressin relations between plasma potassium and the urinary excretions of these ions. 5 Both rates of vasopressin infusion were equally effective in increasing the potassium clearance. Any differences in clearance between the two rates of vasopressin administration were not statistically significant. 6 The large increments in potassium excretion (averaging greater than 40%) were interpreted as indicating that, when vasopressin is present at high concentrations, the distal tubule is one site of action of the hormone in the nephron of sheep.

Kidney development in newborn lambs: Response to water load and antidiuretic hormone (ADH)

Six newborn female lambs were maintained on a formula similar to normal ewe's milk and five on a high protein diet for up to 7 weeks. From the earliest postnatal days a series of urine and blood samples was collected from each lamb twice weekly. The first series of samples was obtained after oral water loading and a second series was collected after ADH administration following an identical water load. Diuretic response to oral water load was as pronounced during the early postnatal days as at 7 weeks. The neonatal ovine kidney was responsive to ADH: ADH administration caused a significant alteration in the diuretic pattern induced by oral water load in the earliest postnatal period studies. There was a marked increase in solute excretion following ADH administration in all lambs. Kidneys of lambs maintained on the high protein diet showed enhanced solute free water reabsorption but also had increased excretion of sodium and potassium following ADH administration.

Impaired renal concentrating ability in hypothyroid man.

The renal concentrating ability was studied in ten patients with hypothyroidism and in 15 euthyroid controls. Solute-free water reabsorption was reduced in the patients with myxedema (4.2 +/- 0.3 ml/min: controls 5.8 +/- 0.6 ml/min; p less than 0.01). This defect was apparent at high rates of solute excretion, and was associated with enhanced excretion of sodium (p less than 0.01) despite a decreased filtered load (p less than 0.005). The myxedema patients had a modest reduction in maximal urine osmolality (p less than 0.04), which was entirely attributable to the lower values observed in younger patients. The results may be explained best by decreased sodium chloride reabsorption in the ascending limb of Henle's loop and/or diminished permeability of the distal nephron in myxedema.

Effect of cold exposure of free water reabsorption in hydropenic man.

With clearance technique, changes in tubular reabsorption of solute free water (TcH2O), were studied in a group of 9 healthy hydropenic volunteers during a cold stress of 1 h at +15 degrees C. Increases were found in TcH2O and in fractional excretion of sodium and osmoles during cold. Since TcH2O was used as an index of sodium reabsorption in the ascending limb of Henle's loop, the findings indicated that under the conditions used in this study, the concentrating ability of the kidney was not negatively influenced by cold, despite a significant increase in arterial pressure. It is suggested that the reabsorption by the ascending limb of the loop was increased secondary to a reduced proximal tubular reabsorption of sodium.

Renal excretion of monovalent cations during functional adrenalectomy in conscious sheep.

In sheep with both adrenals removed and one re-implanted in the neck, functional adrenalectomy was produced in conscious undisturbed animals by occluding the blood supply to the transplanted gland. Functional adrenalectomy caused a fall in potassium excretion and a very large increase in sodium excretion and was reversed by aldosterone. Hydrocortisone infusions slightly increased potassium excretion and reduced solute-free water reabsorption. Preliminary evidence suggests that potassium secretion into urine was still occurring during the 8 hr period of adrenal occlusion and functional adrenalectomy.

Acute effects of lithium on the renal concentrating mechanism in a primate.

Although chronic lithium therapy has been associated with a defect in the urinary concentrating mechanism, short-term renal effects of lithium have received little attention in the intact animal. Solute-free water reabsorption (T-cH2O) and free water clearance (CH2O) were measured in primates of the genus Galago under control conditions and while animals were receiving either 0.5 mmol/kg-h or 1.0 mmol/kg-h lithium chloride (135 mM) intravenously. CH2O was unchanged by lithium infusion (P greater than 0.10), whereas T-cH2O was significantly depressed at all levels of osmolal clearance (P smaller than 0.01). Spontaneous recovery of near-normal T-cH2O was documented in two animals within 1 wk following acute lithium infusion. In addition it was observed that lithium-induced depression of T-cH2O could be partially prevented by pretreatment with intravenous amiloride. These results suggest that alterations in the renal concentrating mechanism can occur rapidly following the onset of lithium administration. They also imply that impairment of the renal concentrating mechanism by lithium is due at least in part to antagonism of the action of vasopressin on the collecting duct.

The urinary concentrating defect in the Gunn strain of rat. Role of bilirubin.

The role of high serum and tissue levels of unconjegated bilirubin in the pathogenesis of the impaired urinary concentrating ability was investigated in homozygous (jj) Gunn rats with the congenital absence of hepatic glucuronyl transferase. Continuous phototherapy with blue fluorescent lights at a wave length of 460 nm or oral cholestyramine feeding or both reduced serum levels of unconjugated hilirubin to levels consistently below 3.0 mg/100 ml for several weeks in both weanling and adult jj Gunn rats. The renal concentrating defect was already present in weanling jj Gunn rats by 21 days of age. In treated weanling jj animals, maximum concentrating ability and the concentration of urea and nonurea solutes in the papilla and medulla, determined after 24 h of fluid deprivation, were normal when compared to unaffected heterozygous (Jj) littermates. Solute-free water reabsorption which is reduced in jaundiced jj Gunn rats was restored to normal in treated weanling jj rats. The tissue concentration of unconjugated bilirubin was reduced throughout the papilla and inner and outer medulla in the treated jj rats in comparison with untreated jj littermates. The defect in urinary concentrating ability was only partially reversible and sometimes irreversible in adult jj rats, probably because of permanent renal parenchymal damage occurring secondary to massive crystalline deposits in the papilla and medulla. It is concluded that unconjugated bilirubin is directly involved in the pathogenesis of the concentrating defect in jaundiced jj Gunn rats.

Renal function in sheep during infusion of alkali metal ions into the renal artery.

1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron.

The sites of action of bumetanide in man

Some pharmacological effects of bumetanide were investigated in 8 healthy volunteers. It was a very potent diuretic, as judged by the fact that, at peak effects during water diuresis, 20% of filtered sodium was excreted in the urine. During water diuresis it reduced free water clearance by approximately 25% and during hydropoenia it reduced the reabsorption of solute free water to a similar extent, indicating a major site of action on the ascending limb of the loop of Henle. A significant phosphaturia was induced during the period of maximum diuresis suggesting an additional action on the proximal tubule. The excretion of urinary titratable acid and ammonium as well as potassium were increased, indicating that the drug did not have a significant effect on sodium transport in the distal tubule. Glomerular filtration rate was not affected but the drug caused a decrease in the renal clearance of uric acid.

Antinatriuresis associated with propranolol administration in the dog.

There is evidence to suggest that the sympatheticnervous system plays a role in the regulation of renal sodium excretion. In the present experiments, the pattern of renal sodium and water excretion following the intravenous infusion of pro pranolol (a β-adrenergic blocking agent) was studied by clearance techniques in nine normal dogs under hydropenic conditions undergoing a modest mannitol diuresis. Blood pressure and pulse rate were monitored throughout. Following systemic administration of propranolol there was a significant decrease in fractional sodium excretion of 2.0 ml/min/100 ml GFR. This occurred despite a 14.2-percent increase in glomerular filtration rate. Potassium excretion and solute-free water reabsorption decreased. There were no significant or predictable changes in heart rate, mean arterial blood pressure, effective renal plasma flow or filtration fraction. These data indicate that propranolol increases renal tubular sodium reabsorption in the dog and suggest that the site of action is in the proximal tubule. Moreover, the data suggest that the mechanism of action is not primarily related to alterations in systemic or renal hemodynamics but may be due to a direct effect on renal tubular sodium transport.

Renal sodium-potassium-activated adenosine triphosphatase and sodium reabsorption.

The role of renal Na(+),K(+)-ATPase in sodium reabsorption was further examined in dogs in which digoxin, a specific inhibitor of the enzyme system, was infused into one renal artery in doses ranging from 0.4 to 0.9 mug/kg/min (low dose) and from 1.0 to 4.0 mug/kg/min (high dose). A significant natriuresis occurred with both dose ranges which was accompanied by inhibition of Na(+),K(+)-ATPase of cortex and medulla in the infused kidney. Despite over 90% enzyme inhibition in many experiments, at least 80% of the filtered sodium continued to be reabsorbed. The per cent change in enzyme activity correlated with the rate of digoxin administration and the total dose administered but not with changes in sodium excretion. Changes in medullary Na(+),K(+)-ATPase activity, however, bore a direct relationship to alterations in fractional solute free water reabsorption (T(c) (H2O)). Inhibition of cortical enzyme activity alone was not associated with natriuresis, suggesting that medullary enzyme activity must be depressed for increased sodium excretion to occur during digoxin infusion. In high-dose experiments, significant inhibition of cortical and medullary enzyme in the contralateral control kidney was also observed, but natriuresis did not occur. In these experiments the rate at which digoxin reached the control kidney rose progressively but never equaled the rates in the directly infused kidney with either dose. Nevertheless, it is clear that under certain circumstances enzyme inhibition of either cortex or medulla need not be accompanied by natriuresis. We conclude that the major role of renal Na(+),K(+)-ATPase is in sodium reabsorption in the medulla (ascending limb of Henle's loop) and that it has a relatively small role in proximal sodium reabsorption. The kidney can rely on other sodium reabsorptive mechanisms depending on the rate of enzyme inhibition, so that natriuresis may not occur at all if depression in activity occurs "slowly." The nature of these mechanisms is not clear.

Prostaglandin (PGA 1), angiotensin and renal function

There may be an important relationship between secretion of prostaglandin(s) and renin in renal physiology since both are found in the kidney. This study was performed to determine whether the prostaglandin, PGA 1, could modify the renal effects of angiotensin. Female mongrel dogs after water deprivation, supramaximal amounts of vasopressin, and desoxycorticosterone (DOCA), were studied during saline diuresis under pentobarbital anesthesia. After a control period, angiotensin II (Hypertensin) and then angiotensin II plus a prostaglandin, PGA 1 (15α-hydroxy-9-oxo-10, 13- trans-prostadienoic acid) were infused via the left renal artery. Angiotensin II in subhypertensive amounts unilaterally and significantly (p<.01, N=36) depressed urine flow (V), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), solute free water reabsorption (T cH 2O), and sodium and potassium excretion in the infused kidney. Subsequent addition of PGA 1 at subhypotensive amounts, unilaterally and significantly (p<.01, N=36) increased V, and ERPF toward control levels while further depressing T cH 2O. No further changes in renal function were observed. The data is compatible with the hypothesis that in the kidney influenced by angiotensin, a prostaglandin, PGA 1, can increase medullary-papillary blood flow, depressing T cH 2O without affecting tubular sodium transport.

Urine concentration during solute diuresis in potassium-depleted rabbits. Evidence for a defect in tubular sodium transport.

1. The relationship between osmolal clearance (C(osm)) and the reabsorption of solute-free water by the kidney (T(H2O) (c)) was examined during 10% mannitol and 2.3% saline diuresis in normal and potassium-depleted rabbits.2. In normal rabbits at osmolal clearances close to 3.0 ml./min, T(H2O) (c) during mannitol diuresis was 0.87 +/- 0.06 ml./min and during saline diuresis 1.19 +/- 0.07 ml./min. The mean difference in T(H2O) (c) of 0.32 +/- 0.05 ml./min was highly significant (P < 0.001).3. In one group of potassium-depleted rabbits with a reduction in maximal urinary concentration, T(H2O) (c) during both mannitol and saline diureses was reduced significantly below normal and the increment in T(H2O) (c) normally seen during saline diuresis was abolished.4. In a second group of potassium-depleted rabbits maximal urinary concentration (1253 +/- 88 m-osmole/kg H(2)O) was not significantly different from that in normal rabbits (1272 +/- 116 m-osmole/kg H(2)O). In these animals, T(H2O) (c) at osmolal clearances close to 3.0 ml./min was not significantly different during mannitol diuresis (0.83 +/- 0.07 ml./min) from that in normal animals, whereas it was reduced significantly during saline diuresis (0.89 +/- 0.07 ml./min, P < 0.001) and the difference in T(H2O) (c) normally seen between mannitol and saline diuresis was abolished.5. The inability to increase T(H2O) (c) during saline diuresis above that achieved during mannitol appears to be the earliest manifestation of the concentrating defect associated with potassium depletion. It probably results from an impairment of sodium transport by the ascending limb of the loop of Henle. This is supported by the fact that potassium-depleted rabbits excreted a greater percentage of the filtered load of sodium than did normal controls.

Effects of hematocrit on renal hemodynamics and sodium excretion in hydropenic and volume-expanded dogs.

The effects of hematocrit on renal hemodynamics and sodium excretion were studied in anesthetized dogs during both hydropenia and volume expansion. The hematocrit was decreased by isovolemic exchange with the animal's own previously harvested plasma and increased by isovolemic exchange with fresh, washed red blood cells. Renal perfusion pressure was maintained constant throughout the experiments by the adjustment of a suprarenal aortic clamp. During hydropenia, a decrease in hematocrit was associated with an increase in sodium and potassium excretion and solutefree water reabsorption. These changes were accompained by an increase in renal plasma flow and renal blood flow and a decrease in renal vascular resistance. Glomerular filtration rate was unchanged and filtration fraction was significantly decreased as hematocrit was lowered. Increasing hematocrit during hydropenia had the opposite effects on electrolyte excretion, solute-free water reabsorption, and renal hemodynamics. In another group of animals, hematocrit was lowered during volume expansion with either saline or plasma, then returned to the control level by isovolemic exchange with washed red blood cells. This increase in hematocrit during volume expansion had a similar effect on electrolyte excretion, solute-free water reabsorption, and renal hemodynamics as during hydropenia. These results therefore suggest that acute changes in hematocrit may significantly affect sodium excretion and renal hemodynamics during both hydropenia and volume expansion. The changes in solute-free water reabsorption and potassium excretion suggest that the alterations in hematocrit may affect primarily the reabsorption of sodium in the proximal tubule. The concommitant effects of hematocrit on renal vascular resistance and filtration fraction may mediate this change in sodium reabsorption by altering hydrostatic and oncotic pressures in the peritubular circulation.

Effect of brief hypercalcaemia on free water reabsorption during solute diuresis: evidence for impairment of sodium transport in Henle's loop.

1. The relationship between osmolal clearance (Cosm) and the reabsorption of solute free water (Tch2o) was examined during mannitol and hypertonic saline diureses in both normocalcaemic and hypercalcaemic rabbits. 2. At high values for Cosm (2–4 ml/min) in normocalcaemic rabbits Tch2o during saline diuresis exceeded that during mannitol diuresis as previously shown. 3. Prolonged hypercalcaemia (72–96 h) reduced Tch2o in both mannitol and saline diureses. 4. Brief hypercalcaemia (18–24 h) abolished the increment in Tch2o normally seen during saline, as compared with mannitol diuresis. This impairment of Tch2o during saline diuresis occurred at a time after the start of hypercalcaemia when Tch2o during mannitol diuresis was still unaffected. 5. The results cannot be attributed to an effect of hypercalcaemia on membrane permeability to water, and are best explained by a reversible limitation of sodium transport in Henle's loop. This interpretation is supported by the fact that the hypercalcaemic rabbits excreted a greater percentage of the filtered sodium load than did the controls.

Urine concentration and dilution in hypokalemic and hypercalcemic dogs.

The urine-concentrating mechanism was studied in chronic hypokalemia (seven dogs given a low K(+), high NaCl diet plus injections of deoxycorticosterone acetate [DOCA]) and chronic hypercalcemia (seven dogs given vitamin D). In the potassium-depleted dogs, muscle, serum, and urine K(+) fell markedly, but glomerular filtration rate (GFR) and body weight varied little. Maximum urine osmolality fell in all dogs (mean decrease = 45%); however, solute-free water reabsorption (T(CH2O)) at high rates of solute excretion remained normal in three of four dogs. Free water excretion (C(H2O)) increased normally or supranormally as a function of increasing Na(+) delivery to Henle's loop in six dogs so tested. Hypercalcemia of several weeks duration caused a decrease in both GFR (mean 36%) as well as in maximum urine osmolality (mean 57%). Maximum T(CH2O) was not invariably depressed; in fact, when the values were adjusted for the reduced number of functioning nephrons (T(CH2O)/C(In)), four of seven studies were normal. C(H20)/C(In) increased normally (or supranormally) with increasing fractional Na delivery to Henle's loop in four of five dogs.I conclude that the lowered maximum urine osmolality in these hypokalemic and hypercalcemic dogs was not related to abnormal water reabsorption from the collecting ducts. Although not specifically measured in this study, it is very likely that solute accumulation in the renal medulla was reduced. This probably was not caused by abnormal delivery of sodium to, nor reabsorption of sodium from Henle's loop. It is likely that a more subtle defect exists in the countercurrent mechanisms for establishing a steep concentration gradient in the renal medulla. In the few hypercalcemic dogs in whom GFR was very low, I believe that injury to, and blockage of medullary tubules could account for most of the reduction in maximum U(Osm). Although not specifically ruled out, there is no evidence here to suggest that high serum Ca(+) or low serum K(+) per se causes a defect in sodium and water reabsorption in the mammalian nephron.

Studies on the exaggerated natriuretic response to a saline infusion in the hypothyroid rat.

The exaggerated natriuresis of hypothyroid rats receiving a 5% saline infusion was studied to determine the mechanism and the site within the nephron responsible for this increase in sodium excretion. Sodium clearance (C(Na)) and fractional sodium excretion were both demonstrated to be greater in hypothyroid rats for any amount of sodium infused. The rate of increase in fractional sodium excretion in response to saline loading was 3.4 times greater in hypothyroid animals. At the conclusion of the diuresis some of the hypothyroid animals excreted greater than 45% of the filtered sodium load, while no control animal excreted more than 12% of the filtered sodium load. The mean clearance of insulin during the saline diuresis was 36.6% lower (P < 0.001) in the hypothyroid rats. D-Aldosterone given to hypothyroid animals 3 hr before the experiment did not alter the magnitude or rate of increase in fractional sodium excretion. Inulin space determinations in nephrectomized rats revealed that extracellular fluid volume was contracted by 17.1% in the hypothyroid rats (P < 0.01). Plasma sodium was not significantly different in hypothyroid and control animals.A limit on solute free water reabsorption (T(e) (H2O)) per osmolar clearance (C(Osm)) was demonstrated in the hypothyroid rats when these animals excreted greater than 12% of the filtered osmotic load. The limit on T(e) (H2O) formation was associated with an acceleration in the rate of sodium excretion and a decline in the rate of potassium excretion. Early in the diuresis when C(Osm), C(Na), and T(e) (H2O) were comparable in hypothyroid and control rats, the filtered sodium load was 31% lower (P < 0.01) in the hypothyroid animals. These findings indicate that diminished thyroid hormone activity decreases renal sodium reabsorptive capacity. Indirect evidence suggests that the distal and possibly the proximal tubules are the sites of this diminished sodium reabsorption in hypothyroid animals.

Intermittent Saline Watering of Growing Beef Heifers

The effects of watering Hereford heifers once/day or once/2 days with tap water (<245 ppm total dissolved solids), 0.50% NaCl or 0.65% NaCl were studied in two summer experiments. Experimental designs were Latin squares with 30-day periods. Total urine was collected on the last 6 days and renal clearance observations were made on the last day. Watering once/day decreased water consumption when compared with ad libitum drinking. Watering once/2 days further decreased consumption, except that consumption of tap water once/2 days was not significantly less than consumption with once/day watering. A prompt and distinct diuresis occurred when the heifers consumed salt water following deprivation. This was not evident with tap water. Renal clearance observations indicate that creatinine, urea-N and solute clearances increased with saline diuresis, but these clearances were not increased following the consumption of tap water. Renal reabsorption of solute-free water increased post-drinking with saline water. It appeared that when saline water was consumed intermittently this water became involved in renal osmoregulation rather than in tissue rehydration.