P-aminohippurate Clearance Research Articles

Elevated urinary prostaglandins and the effects of aspirin on renal function in lupus erythematosus.

We studied the urinary excretion of immunoreactive prostaglandin E-like material (iPGE) and renal function in seven women with systemic lupus erythematosus to evaluate the relation between urinary iPGE and the increase in serum creatinine in patients taking aspirin. The mean pretreatment excretion of urinary iPGE in patients with lupus erythematosus, 42.7 +/- 6.4 ng/h, was significantly higher than the value of 29.0 +/- 1.9 ng/h for normal subjects (P less than 0.02). With aspirin, the urinary iPGE decreased an average of 45% (P less than 0.001). Increases in serum creatinine and blood urea nitrogen confirmed our previous clinical observations. The concomitant mean fall in creatinine clearance of 18% (P less than 0.001) was accompanied by a 14% decrease in inulin clearance (P less than 0.005); p-aminohippurate clearance fell 29% (P less than 0.005). The decline in urinary iPGE preceded the fall in creatinine clearance but was significantly correlated with it (r = 0.78; P less than 0.001). The observed changes reversed rapidly when aspirin was stopped. These data show that, in these patients with high urinary iPGE excretion, aspirin causes significant changes in renal function that may be mediated by the inhibition of prostaglandin synthesis.

Effects of simultaneous infusions of glucagon and cyclic AMP on glomerular filtration rate in the dog

In this study, we tested the hypothesis that the renal vasodilator properties of glucagon are mediated by the intracellular release of cyclic AMP. In eight normal dogs, we tested the effect on glomerular filtration rate (GFR) of intravenous glucagon (5 μg/min), after having administered cyclic AMP (1.6 mg/min) into the left renal artery. GFR for both the right and left kidneys increased by 38% (p < 0.05), compared with an increment of 29% when glucagon alone had previously been administered. Similar studies were carried out in five dogs with steady-state hemorrhagic hypotension (arterial blood pressure = 75 mmHg). In this group as well, the prior infusion of cyclic AMP did not blunt or abolish the tendency of glucagon to promote renal perfusion or increase GFR. When cyclic AMP was administered alone, GFR and the clearance of p-aminohippurate usually declined by about 20% (p < 0.05). In six dogs, glucagon was administered intravenously at 5 μg/min prior to the infusion of cyclic AMP (1.6 mg/min) into the left renal artery. For this kidney, the anticipated decline in renal perfusion occurred. The prior administration of theophylline into the left renal artery did not prevent an intravenous infusion of glucagon from elevating GFR. These experiments indicate that the prior flooding of the microvasculature with either cyclic AMP or glucagon does not prevent the pharmacological effects of each of these substances. The renal hemodynamic effects of glucagon in normal and hypotensive dogs does not appear to depend on the release of cyclic AMP.

Renal and hepatic microsomal enzyme stimulation and renal function following three months of dietary exposure to polybrominated biphenyls

Polybrominated biphenyls (PBB) stimulate microsomal enzyme activity and produce a variety of toxic manifestations, including renal and hepatic histopathological changes. Therefore, it was of interest to determine the effect of chronic exposure to PBB on renal and hepatic microsomal enzyme stimulation and renal function. Adult Sprague-Dawley rats were fed diets containing 0 or 100 ppm of PBB for 3 months. Treatment with PBB retarded weight gain and increased the liver to body weight ratio but did not alter kidney to body weight ratio. Biphenyl-4-hydroxylase (BP-4-OH) and biphenyl-2-hydroxylase (BP-2-OH) activities were elevated in the kidney and liver following treatment with PBB. Exposure to PBB increased aryl hydrocarbon hydroxylase (AHH) activity in the kidney and liver. Epoxide hydratase (EH) activity was increased in the liver but decreased in the kidney following exposure to PBB. A three-month exposure to PBB had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) in thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBB. In conclusion, chronic exposure to PBB resulted in significant alterations in renal and hepatic microsomal enzyme activities but had no detectable effect on renal function. These experiments suggest that alterations in microsomal enzyme activities following PBB do not lead to impairment of renal function; however, this compound may sensitize the kidney to toxicity produced by agents administered subsequent to PBB.

Trimethoprim/sulfamethoxazole and renal function in transplant patients

Twenty-two patients with functioning renal allografts took part in a double-blind crossover trial during which placebo, sulfamethoxazole, and trimethoprim/sulfamethoxazole were given for periods of 14 days. The patients were divided into 2 groups. The first group consisting of 12 patients had serum creatinine levels less than 0.18 mmol/L and the second group of 10 patients had serum creatinine levels between 0.18 mmol/L and 0.35 mmol/L. Renal function at the end of each period was assessed by clearance of inulin (CIn), p-aminohippurate (CPAH) and endogenous creatinine (CCr). The second group also had a pitressin concentration test as a measure of distal tubule function. There was no change in inulin or creatinine clearance or in maximum concentration after pitressin in any of the patients in any of the phases. In the first group there was an increase in PAH clearance during the sulfonamide and trimethroprim/sulfamethoxazole phases. This change was not seen in the second group of patients with significantly impaired renal function.

Lack of a role for the renal nerves in renal sodium reabsorption in conscious dogs.

1. Studies in anaesthetized animals suggest that the renal nerves have a role in the regulation of sodium excretion. Urinary sodium excretion decreases when the renal nerves are stimulated and increases after renal denervation or ganglionic blockade. In order to define the role of the renal nerves in the regulation of urinary sodium excretion in awake animals, dogs were prepared with one kidney denervated and the other intact and the bladder split so that urine could be collected from each kidney. Denervation was confirmed by kidney noradrenaline analysis (1·72 ± 0·29 vs 0·18 ± 0·12 nmol/g). 2. These dogs were studied awake with one of two protocols on each of two separate days. In protocol VH, volume expansion (5% body weight) was followed by haemorrhage of 2% body weight. Fractional sodium excretion fell from 4·7 ± 0·5 to 1·1 ± 0·2% on the denervated side and from 5·6 ± 0·6 to 1·4 ± 0·3% on the intact side. Inulin and p-aminohippurate clearance fell similarly on both sides. 3. In protocol HV, haemorrhage of 2% body weight was followed by blood replacement and volume expansion of 5% body weight. In this second protocol fractional sodium excretion during haemorrhage was 0·23 ± 0·07 and 0·24 ± 0·09% for denervated and intact kidneys respectively and increased to 2·04 ± 0·32 and 2·78 ± 0·60 after volume expansion. 4. In both protocols the denervated kidney was able to reabsorb sodium as well as the innervated kidney during haemorrhage and was able to increase fractional sodium excretion as well as the denervated kidney during volume expansion. These results suggest that the renal nerves do not have a significant role in the regulation of sodium excretion in conscious animals.

Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes.

Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function.

A NEW SIMPLE METHOD FOR OPTIMAL STORAGE OF ISCHEMICALLY DAMAGED KIDNEYS

SUMMARY A new method was developed for sufficient normobaric oxygenation of kidneys during storage in solutions of intracellular ionic composition. Sufficiency of oxygenation by “retrograde oxygen persufflation” was controlled by estimation of cellular metabolic state. SUMMARY In dogs functional recovery of the kidney was tested following autotransplantation after 24 hr of hypothermic persufflation storage, with or without a preceding period of 30 min of normothermic ischemia, and compared with simple storage in Collins' solution or continuous perfusion with albumin solution. Kidney function immediately after transplantation and 24 hr later was determined by inulin and p-aminohippurate clearances for transplanted and contralateral normal kidneys simultaneously. Immediate functional recovery values after persufflation storage amounted to 56 and 46% of the normal contralateral kidney in p-aminohippurate and inulin clearances, respectively, and were similar to the results of continuous perfusion. Furthermore, even after 30 min of normothermic ischemia followed by 24 hr of persufflation storage, the clearance values reached 49 and 32% of the normal values for p-aminohippurate and inulin, respectively, immediately after transplantation. SUMMARY Thus, the method of persufflation storage comines the advantages of storage and continuous perfusion it is simple and cheap like the storage methods but is most effective even in ischemically damaged organs as continuous perfusion.

Influence of basal insulin and glucagon secretion on potassium and sodium metabolism. Studies with somatostatin in normal dogs and in normal and diabetic human beings.

To examine the role of basal insulin and glucagon secretion in potassium and sodium homeostasis, somatostatin, a potent inhibitor of insulin and glucagon secretion, was infused for 5 h into healthy human subjects, maturity-onset diabetes, juvenile-onset diabetics, and normal dogs. Infusion of somatostatin resulted in an increase in serum potassium (0.5-0.6 meq/liter) in normal subjects and maturity-onset diabetics, but not in juvenile-onset diabetics despite equivalent reductions in plasma glucagon in all three groups. A similar rise in serum potassium was observed in normal conscious dogs given somatostatin and was reversed by insulin replacement. Urinary excretion of potassium was unaffected by somatostatin. In dogs given intravenous potassium chloride in doses (0.375 meq/kg per h) which do not alter basal insulin levels, the rise in serum potassium (0.6 meq/liter in controls) increased 100% when somatostatin was administered together with the KCl infusion. Addition of replacement doses of insulin to the somatostatin infusion resulted in increments in serum potassium which were comparable to infusion of KCl alone. Urinary potassium excretion rose after KCl administration and was unchanged by the addition of somatostatin. Serum sodium concentration was unaffected by somatostatin administration in both the human and dog studies. However, urinary sodium excretion displayed a biphasic response falling by 20-60% within the first 2 h of somatostatin administration and then rising to values 50-80% above basal levels at 3-4 h. Inulin and p-aminohippurate clearances were unaffected by somatostatin. It is concluded that (a) potassium homeostasis is influenced by basal insulin levels in the absence of which serum potassium concentration rises and potassium tolerance declines; (b) this effect of insulin is mediated via extrarenal mechanisms of potassium disposal; (c) somatostatin has a biphasic effect on urinary sodium secretion, the mechanism of which remains to be established.

Familial Hypertension and Hormonal Profile, Renal Haemodynamics and Body Fluids of Young Normotensive Subjects

1. Almost all the factors that may cause a rise in blood pressure are, in turn, influenced by the increase in blood pressure per se. Thus any primary involvement of one or more of these factors in the pathogenesis of essential hypertension must be evaluated before or during the development of hypertension. 2. Young normotensive subjects both of whose parents are hypertensive have a much higher probability of developing hypertension than those whose parents are both normotensive. 3. The following measurements were made in 56 subjects of the first group (both parents hypertensive) and 35 of the second group (both parents normotensive), matched for age, sex and body surface area: renal plasma flow and glomerular filtration rate, using p-aminohippurate and inulin clearance; 24 h urinary excretion of aldosterone, protein and electrolytes; plasma renin activity; plasma volume. Plasma catecholamines and cardiac index were also measured in 26 subjects of the first group and 25 subjects of the second group using a radioenzymic method and echocardiography. 4. All these factors were similar in the two groups except that renal plasma flow was higher in the first group (767·2 ± 30 versus 650·7 ± 17 ml/min, P < 0·01). Plasma renin activity tended to be lower in subjects with a higher renal plasma flow, but there was no significant negative correlation between the two factors. 5. The possibility that the higher renal plasma flow in subjects with a high probability of developing hypertension is a compensatory mechanism for a primary intrarenal defect is discussed.

Renal function changes during preoptic-anterior hypothalamic heating in the rabbit.

Thermoregulatory reactions evoked by selective preoptic-anterior hypothalamic (PO/AH) heating in conscious rabbits were associated with significant changes in renal function. Urine flow rate decreased from a control value of 0.92 +/- (S.E.) 0.08 to 0.47 +/- 0.07 ml/min after 10-20 min of heating, urine osmolality increased from 273 +/- 34 to 417 +/- 46 Osm/kg H2O, and free water clearance per 100 ml GFR decreased from 1.11 +/- 0.46 to -0.50 +/- 0.23 ml/min. These changes were followed by a gradual recovery despite continued heating. Clearances of exogenous creatinine and p-aminohippurate fell transiently during the first 10 min of heating and then returned to normal. Plasma antidiuretic activity (ADA) measured by rat bioassay increased regularly and markedly during PO/AH heating but was poorly correlated with changes in urine concentration. Moreover, a similar increase in plasma ADA observed with selective heating of a different brain area (supraoptic nucleus) never produced urine concentration or other renal changes. This suggests that a large and variable fraction of ADA appearing in rabbit blood in response to thermal stimuli was not identical with antidiuretic hormone. Therefore, the causal relationship of ADH release and antidiuresis associated with thermoregulatory reactions could not be clearly demonstrated. The physiological role of renal water conservation would be to compensate for extrarenal water loss related to thermal sweating or panting.

Micropuncture study of fluid transfer in aminonucleoside nephrosis in the rat.

The relationship between glomerular filtration rate and proximal tubular fluid reabsorption was evaluated in control rats and in rats 96 and 144 hr after the injection of an aminonucleoside of puromycin. Urine volume and sodium excretion were decreased in the rats injected with aminonucleoside. Proteinuria increased progressively. Total kidney glomerular filtration rate (GFR) was diminished less than surface nephron GFR at 96 hr and greater than single nephron GFR at 144 hr after injection when a large proportion of nephrons are nonfunctional. Clearance of p-aminohippurate was unchanged initially and depressed subsequently after aminonucleoside injection. Absolute reabsorption to the end of the proximal convolution was unaltered despite a decrease in total kidney filtration fraction. This decrease in GFR coupled with unchanged absolute reabsorption and hence increased fractional proximal reabsorption leads to decreased delivery of sodium and fluid to the more distal portions of the nephron.

The renal handling of 2,4,5-trichlorophenoxy-acetic acid (2,4,5-T) in the dog

The herbicide 2,4,5-T is actively transported by renal cortical slices of dogs and rats, suggesting that the compound should be rapidly eliminated from the body via the kidneys. The prolonged plasma half-life of 2,4,5-T in the dog (77 hr) indicates that factors other than secretion into the urine are important determinants of elimination in the dog. This study was designed to determine the renal handling of 2,4,5-T in anaesthetized dogs, and an attempt was made to increase excretion of the herbicide with sodium acetate. Injection of 2,4,5-T decreased clearance of p-aminohippurate in a dose-dependent manner, suggesting that the compound was actively secreted. The clearance of the herbicide, however, was exceedingly low, being less than 1% of inulin clearance. The clearance of 2,4,5-T was increased by sodium acetate and by acetazolamide. Additional studies with mannitol, sodium bicarbonate and ammonium chloride demonstrated that clearance of 2,4,5-T was related to urinary pH, but only when the pH exceeded 6, and was not affected by changes in urine volume. Addition of plasma inhibited the transport of 2,4,5-T by renal cortex slices in vitro, suggesting that the low clearance in vivo was due to very tight binding of the herbicide to plasma protein.

Effect of diazoxide on renal handling of sodium in the rat.

1. To assess whether diazoxide-induced sodium retention is due to a direct renal action of the durg, independent of its systemic haemodynamic effects, diazoxide was infused directly into one renal artery of hydropenic rats. During the infusion period there was a small fall in mean systemic arterial blood pressure. There were no significant changes in the clearances of inulin or p-aminohippurate by either kidney. 2. Absolute and fractional excretion of sodium were unchanged on the non-infused side. On the side of infusion, there was a significant increase in absolute and in fractional sodium excretion. 3. Thus natriuresis rather than sodium retention seems to be the direct renal effect of diazoxide and may be related to its vasodilator properties.

Changes in renal haemodynamics and electrolyte excretion during acute hyperkalemia in conscious adrenalectomized sheep.

The p-aminohippurate (PAH) clearance, inulin clearance and the excretion of electrolytes by 10 adrenalectomized sheep were measured before, during and after the infusion of 0-43 M-KCl at 2 ml./min for 2 hr. The PAH clearance increased as the plasma potassium concentration increased up to approximately 6-0 m-mole/l. Further increases in plasma potassium were associated with a progressive return of the PAH clearance to or below the pre-infusion levels. At its maximum the PAH clearance was 1-228 +/- 0-032 (S.E. of mean) times the pre-infusion levels. The inulin clearance increased to reach a mazimum coincident with or subsequent to the maximum PAH clearance. The maximum level of inulin clearance during the hyperkalaemia was 1-158 +/- 0-020 times the pre-infusion clearance. The increments in the clearance of potassium and of bicarbonate rose rapidly to exceed the increment in inulin clearance during the hyperkalaemia in all experiments. The increments in the clearance of sodium and of chloride exceeded the increment in inulin clearance in more than half the experiments. It was concluded that although hyperkalaemia was associated with increased glomerular filtration much of the increased excretion of sodium, chloride and bicarbonate was derived from depressed tubular reabsorption of the ions. When the infusion experiments were repeated on the same animals the sheep demonstrated an improved ability to control the rise in plasma potassium concentration which was similar to potassium adaptation described in other species. There were no apparent differences between sheep maintained on 1-5 mg and 5 mg deoxycorticosterone acetate daily in their adaptation to potassium loading and the effect was tentatively attributed to the level of steroid maintenance being chronically high. The toxicity of hyperkalaemia was not lessened by this adaptation to potassium loading.

Vasopressin-Induced Increase in Renal Lymph Flow and Natriuresis in Dogs

1. Renal lymph flow and composition as well as renal haemodynamics and electrolyte excretion were studied in dogs during three experimental periods: control [endogenous antidiuretic hormone (ADH)], water diuresis (low ADH) and during exogenous ADH administration. 2. During water diuresis CPAH and CCr were significantly increased although lymph flow and urinary sodium excretion were unchanged. 3. Infusion of ADH significantly increased renal lymph flow and sodium excretion. However, when compared with values obtained during water diuresis, ADH infusion did not significantly change clearance for p-aminohippurate (CPAH), creatinine (Ccr) and osmolal clearance (Cosm), filtration fraction or net capillary colloid osmotic pressure in dogs forming concentrated urine. 4. It is suggested that a shift of blood flow from vasa recta to outer medullary capillaries, with increased capillary protein leakage and medullary interstitial volume, is responsible for the changes observed in lymph flow and sodium excretion.

Acute effects of cadmium on proximal tubular function in rabbits

Acute renal failure was studied in rabbits 3 days after a single iv injection of a CdCl 2-mercaptoethanol mixture (10 μmol Cd and 350 μmol mercaptoethanol/kg). Glomerular filtration rate (GFR), p-aminohippurate clearance (C PAH), and extraction of p-aminohippurate (E PAH) were severely depressed by poisoning. The lower C PAH and E PAH in poisoned rabbits reflected, at least in part, a cytotoxic action of cadmium on cortical tissue. The filtration fraction, defined as GFR/renal plasma flow (calculated as C PAH E PAH ) also fell. Reabsorption of all amino acids measured was strongly inhibited during the stage of acute renal failure. The site of this inhibition was the luminal membrane of tubule cells, as deduced from the identity of mean artery-to-urine transit times of [ 3H]inulin and 14C-labeled amino acids. In contrast to these tubular dysfunctions, the maximum tubular ability to reabsorb filtered glucose was unaltered, when corrected for changes in GFR, indicating that the effects of cadmium were relatively specific.

The effect of tubular damage by mercuric chloride on kidney function and some urinary enzymes in the dog

Alkaline and acid phosphatases, β-glucosidase, β-galactosidase, N-acetyl- β-glucosaminidase and lactate dehydrogenase were monitored in the urine and serum of dogs with renal tubular damage induced by a series of increasing doses of mercuric chloride. Isocitrate dehydrogenase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase were assayed in the serum. The functional capacity of the kidney was determined by creatinine, inulin and p-aminohippurate (PAH) clearances and tubular maxima tests. Serum urea levels, total protein in the urine and the specific gravity of the urine were monitored throughout the study. The extent and location of the kidney damage was determined by histological investigation. Evidence is presented that the assay of urinary alkaline and acid phosphatase is the most sensitive method of detecting renal tubular damage in the dog. The clearance of [ 14C]-propranolol was compared before and after the administration of mercuric chloride. In the presence of tubular damage the blood half-life of propranolol and the rate of excretion of metabolites in the urine were increased.

The action of bombesin on the kidney of the anaesthetized dog.

1. In the anaesthetized dog bombesin had a potent antidiuretic effect, and sometimes arrested urine flow completely. Threshold doses, by i.v. infusion, were of the order of 0.5-1 (ng/kg)/minute. Antidiuresis was the result of a reduction in glomerular filtration rate provoked by a fall in intraglomerular hydrostatic pressure. This, in its turn, was due to afferent vasoconstriction.2. The spasmogenic effect of bombesin on the smooth muscle of the afferent arterioles was directly demonstrated by the radioactive microspheres technique and indirectly by the (85)Kr washout method and by [(3)H]-p-aminohippurate clearance. The vascular compartment most sensitive to bombesin was that of the outer cortical zone, especially in its external half.3. Filtration fraction decreased under the influence of bombesin, indicating that the effect of the polypeptide on postglomerular arterioles was, if present, only of minor importance.4. At high infusion rates (above 6 (ng/kg)/min), bombesin produced a decrease in [(3)H]-p-aminohippurate extraction. The effect of the polypeptide on fractional distal delivery of sodium varied with the dose: at moderate infusion rates it decreased, at high infusion rates it increased. The total glucose appearing in urine following a glucose load was sharply reduced by bombesin. However, the glomerular filtration rate/maximum tubular glucose transport ratio did not show any appreciable change.5. Afferent vasoconstriction produced by bombesin was accompanied by an intense activation of the renin-angiotensin system, as shown by a conspicuous increase in renin secretion, followed by increases in renin activity and angiotensin II concentration in arterial blood. When bombesin was infused into one renal artery only the infused kidney showed afferent vasoconstriction and increased renin secretion. The time-course of renin secretion produced by bombesin depended upon the rate of infusion of the polypeptide. At low rates an increased renin secretion was observed throughout the infusion period, at high rates two peaks of renin secretion could be seen, one at the beginning of the infusion, the other soon after the infusion had finished.6. The mechanism of action of bombesin is discussed and the interest of the polypeptide as a possible hormonal regulator of the circulation and function of the kidney is pointed out.

Micropuncture study of albumin transfer in aminonucleoside nephrosis in the rat.

The relationship between glomerular filtration rate and proximal tubular fluid reabsorption was evaluated in control rats and in rats 96 and 144 hr after the injection of an aminonucleoside of puromycin. Urine volume and sodium excretion were decreased in the rats injected with aminonucleoside. Proteinuria increased progressively. Total kidney glomerular filtration rate (GFR) was diminished less than surface nephron GFR at 96 hr and greater than single nephron GFR at 144 hr after injection when a large proportion of nephrons are nonfunctional. Clearance of p-aminohippurate was unchanged initially and depressed subsequently after aminonucleoside injection. Absolute reabsorption to the end of the proximal convolution was unaltered despite a decrease in total kidney filtration fraction. This decrease in GFR coupled with unchanged absolute reabsorption and hence increased fractional proximal reabsorption leads to decreased delivery of sodium and fluid to the more distal portions of the nephron.

Renal function in saline-loaded dogs with minimal sodium excretion.

In this laboratory, dogs acutely saline-loaded to 7–8% body weight and treated with large doses of antidiuretic hormone and deoxycorticosterone acetate will excrete on the average 400–700 μequiv/min of sodium. We have been able to study five dogs, similarly treated, which for no apparent cause showed a trivial natriuretic response following comparable volume expansion. Postexpansion sodium excretion varied from 30 to 150 μequiv/min. Glomerular filtration rate and arterial blood pressure remained constant, but in each case p-aminohippurate clearance rate (CPAH) fell in response to acute saline loading. Renal vasodilatation with acetylcholine and elevation of perfusion pressure with noradrenaline reversed the sodium retention. Fractional reabsorption in the proximal tubule was normal, and the loop of Henle appeared to be the major nephron site responsible for the augmented sodium reabsorption. Constancy of arterial blood pressure, fall in CPAH, and response to altered intrarenal hemodynamics seem to characterize these saline-loaded dogs with minimal sodium excretion as a unique population.