Relationship of urinary kallikrein excretion to urinary potassium excretion during furosemide administration with and without amiloride

The relationship of urinary kallikrein excretion to urine volume, and to urinary sodium and potassium excretions was studied in normal rats during furosemide diuresis and superimposed injection of amiloride, a K+-sparing diuretic. Continuous infusion of furosemide increased urinary kallikrein, sodium and potassium excretions and the urine volume. Amiloride injection during furosemide diuresis caused further increase in diuresis and natriuresis, but a prompt decrease in urinary kallikrein excretion to basal level, and potassium excretion to below the basal level. The significant correlation of urinary kallikrein excretion to urinary potassium excretion, but not to urine volume and urinary sodium excretion after amiloride injection suggests that the major determinant of urinary kallikrein excretion is renal potassium secretion through a mechanism that is affected by amiloride.     

Chronic potassium supplementation of newborn dogs increases cortical Na,K-ATPase but not urinary potassium excretion

The distal nephron of the newborn dog cannot secrete an acute potassium load as efficiently as can that of the adult dog. Distal nephron potassium secretion is dependent upon basolateral Na,K-ATPase activity. Because Na,K-ATPase activity is lower in the immature than the mature distal nephron, it was hypothesized that lower Na,K-ATPase activity may be responsible for the lower potassium secretory capacity of the immature nephron. In the adult, chronic high dietary potassium intake increases renal tubular potassium secretory capacity by increasing Na/K pump abundance in distal nephron segments responsible for potassium secretion. Therefore, in order to test the above hypothesis, renal cortical and outer medullary Na,K-ATPase activity under Vmax conditions (a measure of pump abundance) and urinary potassium excretion during acute potassium loading were determined in 7 age-matched, litter mate pairs (chronically potassium supplemented versus control) newborn dogs. The potassium supplemented member of each pair received 6 mmol.day-1.kg-1 of KCl as a 150 mM solution for 7-21 days after birth and the control member received an equal volume of water for the same period of time. This protocol resulted in a doubling of renal cortical Vmax Na,K-ATPase activity in the potassium supplemented animals (from 369 +/- 186 to 718 +/- 286 nmol Pi liberated.h-1.micrograms DNA-1, P = 0.025). There was no significant change in outer medullary enzyme activity. Contrary to the above hypothesis, this increase in cortical enzyme activity was not associated with increased potassium excretion at baseline or during acute potassium loading.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary kallikrein excretion after potassium adaptation in the rat

24-h urinary kallikrein excretion in male Sprague-Dawley rats was measured before and after 14 days with 100 mM potassium chloride as drinking fluid ad libitum. Urinary kallikrein excretion increased in K+-adaptation. The increase was greater when the rats were given distilled water rather than 100 mM sodium chloride to drink prior to the potassium chloride. The urinary potassium excretion increased in all rats studied. The urinary sodium excretion, urine volume and fluid intake increased significantly in rats that had distilled water to drink prior to the KCl. In marked contrast, when rats were offered NaCl prior to KCl, the urinary sodium excretion was unaffected while the urine volume and fluid intake decreased significantly. This study shows that prior NaCl intake abolishes the natriuretic and diuretic effects of KCl load and only suppresses the increase in urinary kallikrein excretion. This suggests that K+ secretory activity at the distal tubules is the major determinant of the release of renal kallikrein in the rat.     

The influence of endogenous mineralocorticoids on the composition of fetal urine

Experiments were carried out in 10 chronically catheterised fetal sheep aged 121-128 days. In 3 animals infusion of aldosterone (5 micrograms/h) caused a fall in fetal urinary Na/K ratio; an effect that was reversed by spironolactone 2.5 mg/kg followed by an infusion of 100 micrograms/h per kg. In 9 fetal sheep which had no previous treatment the same doses of spironolactone had no effect on fractional sodium excretion although the fractional excretion of potassium decreased (P less than 0.05) and the urinary sodium potassium (Na/K) ratio rose (P less than 0.05). Amiloride had a variable effect on sodium excretion but the fractional excretion of potassium decreased markedly (P less than 0.05). Thus in chronically catheterised fetal sheep, endogenous mineralocorticoid activity altered urinary potassium excretion and the urinary Na/K ratio. However this activity was low, as distal blockade with amiloride further decreased the fractional excretion of potassium and increased the urinary Na/K ratio.     

The effect of isoproterenol on fluid and electrolyte transport in the inner medullary collecting duct

In the late distal and cortical collecting tubule, which is the principal regulatory site for potassium (K) excretion, vasopressin stimulates, and epinephrine via beta-adrenergic action, inhibits K secretion. In the inner medullary collecting duct (IMCD) we have shown that vasopressin also stimulates K secretion. The present experiments were designed to determine whether the beta-adrenergic agonist, isoproterenol, would induce K reabsorption in the IMCD, and (or) prevent a secretory response to acute KCl infusion. Two groups of rats, with or without isoproterenol administration (3 micrograms/h), were subjected to retrograde microcatheterization of the IMCD before and during infusion of 0.83 mol/h KCl. Isoproterenol reduced plasma K concentration and urinary K excretion, but the response to acute KCl infusion was qualitatively similar to control. Isoproterenol decreased delivery of potassium, chloride, and fluid to the IMCD, there was no net transport of K along the duct in either group, and KCl infusion did not result in K secretion in either group. The results indicate that isoproterenol may inhibit K secretion in the late distal or cortical collecting tubule. However, there was no statistically significant difference in K transport along the IMCD between isoproterenol and control groups. Reduced sodium excretion, which was found during isoproterenol administration both before and after KCl infusion, was associated with no change in sodium delivery but with increased sodium reabsorption in the IMCD. This increased sodium reabsorption may be a direct effect of isoproterenol, or may be due to reflex cardiovascular adjustments associated with systemic actions of the drug.     

Effects of aldosterone and corticosterone on cloacal water and electrolyte excretion of constantly-loaded intact and colostomized ducks (Anas platyrhynchos)

1. Doses of aldosterone (50, 100 and 200 micrograms per kg body wt) evoked similar changes in Na+ and K+ excretion by intact and colostomized ducks loaded with either distilled water or 0.5 isotonic saline (70 mM NaCl, 1.5 mM KCl); both antinatriuretic and antikaliuretic responses were observed. 2. The lowest dose of aldosterone had no effect on electrlyte excretion in intact and colostomized ducks loaded with a solution containing more K+ than Na+ (74 mM KCl, 36 mM NaCl) but the higher doses caused an antinatriuretic response in both groups; a retention of K+ occurred only in intact birds given this solution. 3. The lower dose of corticosterone (1.25 mg per kg body weight) caused both antidiuresis and antinatriuresis in intact birds, but in colostomized birds the decrease in Na+ excretion was not accompanied by an antidiuresis. 4. The higher dose of corticosterone (2.50 mg per kg body wt) caused a significant increase in K+ excretion in colostomized birds, whereas no kaliuresis was ever observed in intact birds. 5. Intact and colostomized birds loaded with 0.5 isotonic saline showed no responses to the lower dose of corticosterone, whereas the higher dose had an antikaliuretic effect in intact birds and an antinatriuretic effect in colostomized birds. 6. Corticosterone had no effect on cloacal water and electrolyte excretion by intact and colostomized birds given loads containing more K+ than Na+.     

Fluoride reabsorption by nonionic diffusion in the distal nephron of the dog

This study was done to test the hypothesis that fluoride reabsorption is extensive from the distal nephron, the major site for tubular fluid acidification, and to compare the distal nephron handling of fluoride and chloride. Ten stop-flow studies were done in five dogs anesthetized with pentobarbital. Urinary alkalinization was achieved by the intravenous infusion of sodium bicarbonate and acetazolamide or lithium chloride. Acidification was achieved by the infusion of sodium nitrate or sodium sulfate. The results indicate that the extent of fluoride reabsorption from the distal nephron is inversely correlated with urinary pH (P less than 0.001). When the urine was strongly acidified by the infusion of sodium sulfate, urine to plasma fluoride concentration ratios were less than 1.0, a finding not previously reported from studies of the renal handling of fluoride. The reabsorption of fluoride from the distal nephron was not correlated consistently with that of chloride. The results indicate that the distal nephron is an important site for the reabsorption of fluoride and they provide additional evidence that HF is the permeating moiety.     

Hepatoportal bumetanide-sensitive K(+)-sensor mechanism controls urinary K(+) excretion

To determine whether a K(+)-sensor mechanism exists in the hepatoportal region, periarterial hepatic afferent nerve activity responses to intraportal injection of KCl were examined in anesthetized rats. Hepatic afferent nerve activity increased in response to intraportal injection in a K(+) concentration-dependent manner, and the increase was attenuated by inhibition of the Na(+)-K(+)-2Cl(-) cotransporter by bumetanide in a dose-dependent manner. These results suggest that a bumetanide-sensitive K(+)-sensor mechanism exists in the hepatoportal region. Stimulation of this mechanism by intraportal KCl infusion elicited an immediate and powerful kaliuresis with no significant change in the plasma K(+) concentration; this was significantly greater than the kaliuresis induced by intravenous KCl infusion and was attenuated by severing the periarterial hepatic nervous plexus. These results indicate that a hepatoportal bumetanide-sensitive K(+)-sensor mechanism senses the portal venous K(+) concentration and that stimulation of this sensor mechanism causes kaliuresis, which is mainly mediated by the periarterial hepatic nervous plexus.     

Effects of low-potassium diet on N-ethylmaleimide-sensitive ATPase in the distal nephron segments.

The present study was undertaken to investigate whether or not potassium deficiency influences N-ethylmaleimide (NEM)-sensitive ATPase in the distal nephron segments of the rat. One group of animals was fed a low-K diet, whereas the normal K-group was given the same diet after supplementation with KCl. The nephron segments examined were: the medullary and cortical thick ascending limbs, the distal convoluted tubule, and the cortical, outer and inner medullary collecting ducts. NEM-sensitive ATPase activity in microdissected segments was measured by a fluorometric microassay. The plasma K+ concentration in the low-K group was 3.1 +/- 0.3 mEq/l compared with 4.2 +/- 0.1 mEq/l in the normal-K group. NEM-sensitive ATPase activity in the outer medullary collecting duct of low-K diet animals was significantly greater than in normal-K animals. There was no significant difference in NEM-sensitive ATPase activity between the two groups of animals in the other nephron segments examined. It is suggested that NEM-sensitive H-ATPase activity in the outer medullary collecting duct is modulated by the potassium status of the animal.     

Cooperative mechanisms of acute antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus

The exact mechanism underlying thiazides-induced paradoxical antidiuresis in diabetes insipidus is still elusive, but it has been hypothesized that it is exerted either via Na+-depletion activating volume-homeostatic reflexes to decrease distal delivery, or direct stimulation of distal water reabsorption. This study examined how these two proposed mechanisms actually cooperate to induce an acute bendroflumethiazide (BFTZ)-antidiuretic effect in nephrogenic diabetes insipidus (NDI). Anaesthetized rats with lithium (Li)-induced NDI were prepared in order to measure their renal functional parameters, and in some of them, bilateral renal denervation (DNX) was induced. After a 30 min control clearance period, we infused either BFTZ into 2 groups, NDI+BFTZ and NDI/DNX+BFTZ, or its vehicle into a NDI+V group, and six 30 min experimental clearance periods were taken. During BFTZ infusion in the NDI+BFTZ group, transiently elevated Na+ excretion was associated with rapidly increased urinary osmolality and decreased free water clearance, but Li clearance and urine flow declined in the later periods. However, in the NDI/DNX+BFTZ group, there was persistently elevated Na+ excretion with unchanged Li clearance and urine flow during the experimental period, while alterations in free water clearance and urinary osmolality resembled those in the NDI+BFTZ group. In conclusion, BFTZ initially exerted two direct effects of natriuresis-diuresis and stimulating free water reabsorption at the distal nephron in NDI, which together elevated Na+ excretion and urinary osmolality but kept the urine volume unchanged in the first hour. Thereafter, the resultant sodium depletion led to the activation of neural reflexes that reduced distal fluid delivery to compensate for BFTZ-induced natriuresis-diuresis which, in cooperation with the direct distal BFTZ-antidiuretic effect, resulted in excretion of urine with a low volume, high osmolality, and normal sodium.     

Treatment of congenital nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride in an adult patient

AIM: The effects of treatment with hydrochlorothiazide (HCTZ) combined with amiloride were elucidated and compared to HCTZ treatment alone and combined with acemetacin or triamterene in a Japanese adult patient with congenital nephrogenic diabetes insipidus. METHODS: The study was divided into seven periods: (1) HCTZ and acemetacin; (2) control period; (3) HCTZ; (4) a second control period; (5) HCTZ and amiloride; (6) a third control period, and (7) HCTZ and triamterene. Fluid intake, urine volume, urinary Na, K, creatinine, and osmolality and serum Na, K, Cl, CO2, and osmolality were measured, and free water clearance and proximal and distal tubular Na reabsorption rates were calculated. RESULTS: Without drug administration, the urine volume was about 8,000 ml/day. The urine volume was reduced to about 6,000 ml/day with HCTZ. A further urine volume reduction to about 5,000 ml/day was obtained with the second drug administration, and the effects were similar among the three regimens. Serum and urinary osmolality and free water clearance were also similar among the three combinations, whereas the urinary potassium excretion was the least, and the serum potassium concentration was the highest with HCTZ plus amiloride. Besides, no alkalosis was observed only with this combination. CONCLUSION: HCTZ plus amiloride may be superior to HCTZ plus acemetacin and HCTZ plus triamterene in preventing hyperkaliuria, hypokalemia, and metabolic alkalosis.     

Effect of lithium on water and electrolyte metabolism.

Studies were performed in the rat to determine the effect of lithium on electrolyte transport in distal portions of the nephron since steep corticomedullary gradient for lithium has been demonstrated and ionic competition and/or substitution of lithium for sodium and potassium may play a role in inhibition of vasopressin-induced water transport. During the intravenous infusion of LiC1, in the absence of volume expansion and at plasma levels of 2-5 mequiv/liter of Li, maximum urine con-entration was inhibitied. Under the same conditions lithium administration impaired potassium secretion and urinary acidification and resulted in a natriuresis. These results indicate that lithium affects electrolyte transport in the same nephron segments in which the action of vasopressin is inhibitied. In addition, evidence is provided that suggests that during the chronic administration of LiC1, the sustained increase in oral intake of water and urinary flow rate results from an increase in thirst as well as reduced renal concentrating ability.     

Potassium excretion during antinatriuresis: perspective from a distal nephron model

Renal excretion of Na(+) and K(+) must be regulated independently within the distal nephron, but is complicated by the fact that changing excretion of one solute requires adjustments in the transport of both. It is long known that hypovolemia increases Na(+) reabsorption while impairing K(+) excretion, even when distal Na(+) delivery is little changed. Renewed interest in this micropuncture observation came with identification of the molecular defects underlying familial hyperkalemic hypertension (FHH), which also increases distal Na(+) reabsorption and impairs K(+) excretion. In this work, a mathematical model of the distal nephron (Weinstein AM. Am J Physiol Renal Physiol 295: F1353-F1364, 2008), including the distal convoluted tubule (DCT), connecting segment (CNT), and collecting duct (CD), is used to examine renal K(+) excretion during antinatriuresis. Within the model, Na(+) avidity is represented as the modulation of DCT NaCl reabsorption, and the K(+) secretion signal is an aldosterone-like effect on principal cells of the CNT and CD. The first model prediction is that changes in DCT NaCl reabsorption are not mediated by NaCl cotransporter density alone, but require additional adjustments of both peritubular Na-K-ATPase and KCl cotransport. A second observation is that the CNT response to increased DCT Na(+) reabsorption should not only stabilize CD K(+) delivery but also compensate for the compromise of K(+) excretion downstream, as low Na(+) delivery increases CD K(+) reabsorption. Such anticipatory regulation is seen with the aldosterone response of hypovolemia, while the FHH phenotype manifests enhanced DCT NaCl transport but a blunted aldosterone effect. The model emphasizes the need for two distinct signals to the distal nephron, regulating Na(+) excretion and K(+) excretion, in contrast to a single switch apportioning NaCl reabsorption and Na(+)-for-K(+) exchange.     

The ATP4- receptor-operated ion channel of human lymphocytes: inhibition of ion fluxes by amiloride analogs and by extracellular sodium ions.

Extracellular ATP is known to increase the membrane permeability of a variety of cells. Addition of ATP to human leukemic lymphocytes loaded with the Ca2+ indicator, fura-2, induced a rise in cytosolic Ca2+ concentration which was attenuated or absent in NaCl media compared with KCl, choline Cl, or NMG Cl media. In contrast, anti-immunoglobulin antibody gave similar Ca2+ transients in NaCl and KCl media. A half-maximal inhibition of peak ATP-induced Ca2+ response was observed at 10-16 mM extracellular Na+. Basal 45Ca2+ influx into lymphocytes was stimulated 9.6-fold by ATP added to cells in KCl media, but the effect of ATP was greatly reduced for cells in NaCl media. Hexamethylene amiloride blocked 74% of the ATP-stimulated Ca45 uptake of cells in KCl media. Flow cytometry measurements of fluo-3-loaded cells confirmed that the ATP-induced rise in cytosolic Ca2+ was inhibited either by extracellular Na+ or by addition of hexamethylene amiloride. Extracellular ATP stimulated 86Rb efflux from lymphocytes 10-fold and this increment was inhibited by the amiloride analogs in a rank order of potency 5-(N-methyl-N-isobutyl)amiloride greater than 5-(N,N-hexamethylene)amiloride greater than 5-(N-ethyl-N-isopropyl)amiloride greater than amiloride. ATP-induced 86Rb efflux showed a sigmoid dependence on the concentration of ATP and Hill analysis gave K1/2 of 90 and 130 microM and n values of 2.5 and 2.5 for KCl and NaCl media, respectively. However, the maximal ATP-induced 86Rb efflux was 3-fold greater in KCl than in NaCl media. Raising extracellular Na+ from 10 to 100 mM increased ATP-induced Na+ influx from a mean of 2.0 to 3.7 nEq/10(7) cells/min, suggesting either saturability or self-inhibition by Na+ of its own influx. These data suggest that ATP opens a receptor-operated ion channel which allows increased Ca2+ and Na+ influx and Rb+ efflux and these fluxes are inhibited by extracellular Na+ ions as well as by the amiloride analogs.     

Long-Term Responses to Loss of Renal Mass: Tubular Changes: Potassium Adaptation After Reduction of Nephron Population

Two weeks after 75 percent nephrectomy in rats fed a normal diet glomerular filtration rate was found to be reduced by 2/3 and there was no hyperkalemia. Normal K balance was maintained by a threefold increase of fractional urinary potassium excretion. When infused with 0.5 M KCl solution, both normal and 75 percent nephrectomized rats increased their fractional excretion, while normal rats kept on a very high K-diet did not further increase their fractional potassium excretion. Adaptation of fractional excretion to infused KCl was blunted in 75 percent nephrectomized rats given a low K diet.Addition of 0.1 M KCl to the drinking water resulted in a three- to fourfold increase of potassium intake in normal rats: within 7 days, the Na-K-ATPase in the outer medulla of the kidney rose by 30 percent but no change occurred in the cortex. Further increases in dietary K load induced an increase of Na-K-ATPase activity, both in outer medulla and cortex, but not in other tissues. After 75 percent nephrectomy, specific Na-K-ATPase activity increased by 20-25 percent in the outer medulla and in the cortex.Dietary K loading, in normal rats, also resulted in a large increase of net potassium secretion into the perfused colon and of specific Na-K-ATPase activity of the colonic mucosa. These effects of potassium loading were not abolished by adrenalectomy and were accompanied by an increase of transmural PD. It was concluded that chronic potassium loading may enhance secretion of potassium into lower nephron tubular fluid and into colonic contents by primarily stimulating the synthesis of Na-K-ATPase and the resulting increase of the number of pumping sites. 75 percent nephrectomy may induce similar changes in the remaining nephrons.     

A stop-flow study of intrarenal effects of atrial natriuretic factor

We performed paired series of stop-flow studies on six mongrel dogs to determine a possible nephron site of action of synthetic atrial natriuretic factor (ANF). The initial free-flow response to intrarenal infusion of 5 micrograms/min of synthetic ANF into mannitol-expanded dogs resulted in an increased urine flow rate (6.81 +/- 0.88 to 9.00 +/- 1.17 ml/min, P less than 0.05) and a 40% increase in sodium excretion (496 +/- 110 to 694 +/- 166 meq/min, P less than 0.025) when compared to paired control periods. Renal blood flow did not change, but the glomerular filtration rate increased 4% (47 +/- 5 to 49 +/- 6 ml/min, P less than 0.05). The filtered load of sodium increased 4% (P less than 0.05), and the fractional sodium excretion increased by 35% (P less than 0.01). Stop-flow experiments showed no difference in tubular sodium concentration or in the fractional sodium-to-inulin ratio at the nadir of sodium concentration, suggesting that no differences existed in distal tubular sodium handling. Further, no apparent differences were detected in collections representing the more proximal portions of the nephron. While we were able to demonstrate marked natriuresis in response to synthetic ANF, no tubular effect was discernible, and the natriuresis obtained appears to be predominantly a function of hemodynamic effects.     

The effect of Ringer solution induced extracellular volume expansion on kidney function

The present study quantitated the effects of extracellular volume expansion on sodium and water excretion in 118 anesthetized dogs. The animals received a priming injection of 10 ml kg-1 Ringer solution i.v. which was followed by a constant Ringer solution infusion at a rate of 0.25 ml.min-1.kg-1 until the end of the experiment. Fifteen minutes after the start of the constant infusion the renal parameters were examined in 11 subsequent 15 min periods (the total time was 3 hours). Volume expansion produced no significant change in arterial blood pressure, glomerular filtration rate (GFR), plasma sodium and potassium concentration or, haematocrit, but did reduce the CPAH from 284 ml.min-1 to 218 ml.min-1 (the data were calculated for 100 gram wet kidney weight). There were constant significant increases in the urinary excretion rate from 0.84 ml.min-1 to 4.06 ml.min-1 and the 39% of the infused water was excreted during the experiment. Volume expansion also caused a significant increase in sodium excretion during the three first periods from 120 mumol.min-1 to 329 mumol.min-1 followed by a small but significant decrease. The sodium excretion at the end of the experiment was 221 mumol.min-1 and the 23% of the infused sodium was excreted in the course of the experiment. The increase of the water excretion during the volume expansion was associated with fall of the urine osmolality and the urine because hypoosmotic as compared to the plasma. We have provided evidence that vasopressin was not involved in the control of water excretion in our experiments. It is concluded that neither filtered sodium nor decreased aldosterone secretion can account for the increase in sodium excretion that occurs after Ringer solution loading in the dog. It has been proposed that a decrease in plasma protein concentration may decrease passive sodium reabsorption due to oncotic forces in the proximal tubule. The Ringer solution diuresis elicits a rise in medullary blood flow, thereby causing a washout of medullary sodium. This might dissipate the osmotic force for the back-diffusion of water from the collecting duct. Our studies indicate that the response of the diluting segments of the distal nephron to increased delivery of sodium depends upon the presence or absence of volume expansion. However the increase of the distal tubular loading activates the tubuloglomerular feedback which increases the proximal tubular reabsorption. Based on these assumptions our studies provide further evidence that the tubuloglomerular feedback regulates the blood pressure in the peritubular capillaries in the cortex around the proximal tubules.     

Renal kallikrein: its localization and possible role in renal function.

The distribution of kallikrein in dog kidneys was studied. It was found that kallikrein decreased from the outer to the inner cortex and that the medulla and papilla had very little kallikrein. The site of kallikrein secretion in the nephron was also studied by performing stop-flow techniques in dogs. The highest kallikrein concentration was found in the fractions with the lowest sodium concentration. It was concluded that kallikrein is secreted into the urine at the level of the distal tubule by either the tubule itself or by a structure related to this part of the nephron. In addition, the possible involvement of the kallikrein-kinin system in the regulation of sodium excretion was investigated. Circulating kinins and urinary kallikrein were increased in saline-loaded dogs. Urinary kallikrein also increased in dogs that have "escaped" the sodium-retaining effect of desoxycorticosterone. Experiments in rats with different sodium intake showed a relationship between water and sodium excretion and urinary kallikrein. These data suggest that the kallikrein-kinin system could participate in the regulation of the renal function at the level of the distal tubule or collecting duct.     

A search for a defect of proximal transport in denervated kidneys of conscious dogs

The influence of renal nerves on proximal Na+ reabsorption was studied in clearance experiments with unilaterally renal-denervated conscious dogs prepared by surgical bladder division. Two types of experiments were made : A. maximal water diuresis, and B. Total blockade of distal NaCl reabsorption with ethacrynic acid and chlorothiazide. In maximal water diuresis CH2O + CNa was used as a measure of fluid delivery to the distal nephron. At similar GFR on both sides, the proximal reabsorption estimated as GFR--(CH2O + CNa) was 38.4 +/- 5.6 ml/min for the intact and 35.9 +/- 4.2 ml/min for the denervated kidney (n = 6, difference NS). After distal tubular blockade, proximal Na+ reabsorption calculated as filtered load minus urinary excretion was 3.84 +/- 0.43 mmol/min for the intact and 3.91 +/- 0.36 mmol/min for the denervated kidney (n = 6, difference NS). The fractional reabsorption of NA+ was 64.9 +/- 1.0% for the intact and 66.9 +/- 1.1% for the denervated kidney (difference NS). In contrast to data from renal denervation studies with anaesthetized animals, the present experiments did not show any difference in proximal reabsorption between the innervated- and denervated kidney. We conclude that in absence of anaesthesia renal efferent nerves have no major effect on NaCl transport in dog proximal tubule.