Micropuncture studies of glucose transport in the dog: mechanism of renal glycosuria

Clearance and micropuncture studies were performed in 23 dogs without glucose loading to examine the tubule mechanism of renal glycosuria. Studies were carried out in three groups of animals before and after 10% extracellular volume expansion, and administration of maleic acid in low dose at 150 mumol/kg and in high dose at 300 mumol/kg. Specific hexokinase methods were used for the determination of glucose in tubule fluid and urine. Under control conditios, glucose reabsorption occurred predominantly in the proximal tubule. In all three groups, proximal tubule reabsorption of both sodium and glucose was inhibited in the second phase, showing a good correlation between the two. In contrast, fractional urinary glucose excretion remained unchanged after volume expansion and low-dose maleic acid, indicating reabsorption of virtually all the increased glucose load at a further "distal" site. On the other hand, significant glycosuria developed after high-dose maleic acid that was a result of reduced glucose reabsorption in the distal nephron, in addition to the proximal effect. It was concluded that distal glucose transport plays a significant role in regulating urinary glucose excretion and maintains renal thershold for glucose,     

Renal responses of the fetal lamb to fetal or maternal volume expansion

Fetal and maternal glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, sodium excretion, and fractional sodium reabsorption were measured in a chronically instrumented sheep preparation. Fetal GFR was essentially stable between 110 and 135 days of gestation (term = 147 days). There was a significant increase in GFR after 135 days. After the infusion of 50 ml of normal saline over a 30-minute period, fetal GFR and sodium excretion increased significantly. Fractional sodium reabsorption was significantly decreased. Thus, the fetus is capable of responding to volume expansion with saline with an increase in GFR and a decrease in fractional sodium reabsorption. After the infusion of 1000 ml of normal saline into the ewe in 1 hour, maternal GFR and RPF rose significantly. Sodium excretion rose 6-fold and fractional sodium reabsorption fell significantly. After the infusion of saline into the ewe, there was no change in fetal GFR, RPF, sodium excretion, urine volume, or fractional sodium reabsorption. Since there were no changes in fetal renal function after maternal volume expansion with saline there was no evidence for the transplacental passage of a natriuretic factor from ewe to fetus.     

The impact of rejection episodes during acute tubular necrosis--diagnosis and allograft outcome after cadaveric renal transplants]

1. We investigated whether diuresis and natriuresis induced by endogenous atrial natriuretic peptide (ANP) were blunted during rapid cardiac pacing. 2. Changes in plasma ANP, renal function and haemodynamics during rapid cardiac pacing were studied in anaesthetized closed-chest dogs. Dogs were paced via the right ventricle at a rate of 200 b.p.m. (moderate pacing) or 250 b.p.m. (severe pacing) for 180 min. 3. The maximal increases in plasma ANP and urinary excretion of cGMP during severe pacing were four- and three-fold higher, respectively, than those during moderate pacing. Despite the higher concentration of plasma ANP, the maximal increases in urine volume, urinary excretion of sodium and fractional excretion of sodium during severe pacing were similar to those during moderate pacing. Mean arterial pressure and renal vascular resistance were decreased only by severe pacing. The increase in total peripheral resistance during severe pacing was significantly smaller than that during moderate pacing. However, the glomerular filtration rate was kept at basal levels by both moderate and severe pacing. 4. These results suggest that there are certain mechanisms that counteract renal tubular sodium reabsorption induced by endogenous ANP under conditions of severe pacing. The suppression occurs at tubular sites but at glomerular sites. One of the possibilities for the suppression is the decrease in renal perfusion pressure accompanied by decreases in peritubular capillary hydrostatic pressure.     

Performance of the lift ventricle in left ventricular obstructive cardiomyopathy

Whether volume expansion influences NaC1 reabsorption by the diluting segment of the nephron remains a matter of controversy. In the present studies this question has been examined in normal unanesthetized dogs, undergoing maximal water diuresis. Free water clearance (CH2O/GFR) has been used as the index of NaC1 reabsorption in the diluting segment. Three expressions have been employed for "distal delivery" of NaC1: a) V/GFR, designated as the "volume term"; b) (CNa/GFR + CH2O/GFR), the "sodium term;" and c) (CC1/GFR + CH2O/GFR), the "chloride term". The validity of these terms is discussed. Three techniques were used to increase distal delivery: 1) the administration of acetazolamide to dogs in which extracellular fluid (ECF) volume was not expanded (grop 1); 2) "moderate" volume expansion (group 2); and 3) "marked" volume expansion (group 3). CH2O/GFR increased progressively with rising values for "distal delivery" regardless of which term was used to calculate the latter. With all three delivery terms, differences in distal NaC1 reabsorption emerged between the two volume-expanded groups, though only with the "chloride" term did substantial differences also emerge between the nonexpanded group 1 dogs and both volume-expanded groups. In group 1, values for CH2O/GFR increased in close to a linear fashion up to distal delivery values equal to 24% of the volume of glomerular filtrate. However, at high rates of distal delivery the rate of rise of CH2O/GFR was less in group 2 than in group 1 and the depression of values was even greater in group 3. Within the limits of the techniques used, the data suggest that volume expansion inhibits fractional NaC1 reabsorption in the diluting segment of the nephron in a dose-related fashion. The "chloride" term was found to be superior to the "volume" and "sodium" terms in revealing these changes.     

An oral glutamine load enhances renal acid secretion and function

In a recent study, a small oral glutamine load acutely elevated plasma bicarbonate concentrations in healthy adults (Am J Nutr 1995;61:1058-61). The present study was designed to elucidate the renal mechanism underlying the base-generating response to L-glutamine. Accordingly, vehicle (489 mL diet soda) or vehicle plus 2 g L-glutamine (28 mg/kg body wt) was ingested and the gain in extracellular fluid volume bicarbonate was compared with renal acid elimination as either ammonium excretion or tubular acid secretion (titratable acid plus bicarbonate reabsorption). Vehicle alone, which contained 27 mmol acid, did not increase extracellular fluid volume bicarbonate over the 90-min period. In contrast, L-glutamine increased plasma bicarbonate concentration (from 25.4+/-2 to 27.9+/-1 mmol/L, P < 0.05) and extracellular fluid volume bicarbonate by an estimated 39+/-10 mmol. When added to that required to neutralize the ingested acid, the combined total for new bicarbonate generated gave an estimated 66+/-10 mmol. Surprisingly, ammonium excretion accounted for < 2% of this newly generated bicarbonate. However, acid secreted and excreted as net acid (5.2+/-4.0 mmol/90 min) as well as that coupled to enhanced bicarbonate reabsorption (76+/-20 mmol/90 min) readily accounted for the estimated base gain (81+/-24 compared with 66+/-10 mmol/90 min). Concomitant with enhanced renal acid secretion, the oral glutamine load elicited an increase in glomerular filtration rate. These results rule out a role for L-glutamine as a direct precursor of bicarbonate and instead point to an indirect role in accelerating acid secretion, apparently coupled to increased glomerular filtration rate.     

Intracerebroventricular neuropeptide Y increases gastric and pancreatic secretion in the dog

BACKGROUND: Neuropeptide Y (NPY), a centrally located neurotransmitter, is known to increase appetite in fasted and satiated animals. In addition to evaluating NPY's effect on eating behavior, this study was intended to determine whether intracerebroventricular (ICV) NPY would have an effect on canine gastric and pancreatic secretion. METHODS: Four dogs were prepared with cerebroventricular guides and gastric and pancreatic fistulas. ICV and intravenous NPY was administered during intragastric titration of a glucose and peptone meal. During this study, gastric and pancreatic secretion was measured, as well as insulin levels and pancreatic polypeptide (PP). An additional set of four dogs were prepared with esophageal fistulas and cerebroventricular guides, and the effect of ICV NPY on sham feeding was studied. RESULTS: ICV NPY significantly increased sham feeding, meal-stimulated gastric and pancreatic secretion, basal gastric acid, pancreatic bicarbonate, insulin levels, and PP. Vagotomy blocked the effect of ICV NPY on gastric acid secretion in a urethane-anesthetized rat model with acute gastric fistula. CONCLUSIONS: ICV NPY increased sham feeding, gastric and pancreatic secretion, insulin levels, and PP in the dogs. NPY's effect on gastric secretion was blocked by vagotomy in a rat model. NPY should be considered a candidate mediator of cephalic phase secretion.     

The identification of Class III malocclusions by discriminant analysis

Atrial natriuretic factor (ANF), a cardiac peptide hormone with potent natriuretic and vasodilator actions, mediates its biologic responses via increases in intracellular cyclic guanosine monophosphate (cGMP). Recognizing that phosphodiesterases degrade cGMP and that congestive heart failure (CHF) is characterized by reduced renal responses to ANF, the authors hypothesized that cGMP phosphodiesterases limit the renal actions of exogenous and endogenous ANF in the presence of experimental CHF. In anesthetized dogs with severe CHF and avid sodium retention produced by rapid ventricular pacing, the authors explored the renal actions of M&B 22,948 (Rh?ne-Poulenc, Essex, UK), an inhibitor of cGMP-specific phosphodiesterases. High-dose intrarenal cGMP phosphodiesterase inhibition (PDI), with minimal effects upon systemic hemodynamics and hormones, significantly enhanced sodium excretion. This occurred primarily by decreasing distal nephron sodium reabsorption while enhancing renal cGMP generation. In separate groups of dogs, low-dose intrarenal cGMP PDI potentiated the actions of exogenous ANF on glomerular filtration and distal nephron sodium reabsorption, leading to enhanced natriuresis in the presence or absence of severe CHF. These studies support a link between ANF and the renal actions of cGMP PDI, and indicate that cGMP phosphodiesterases may contribute to sodium retention in advanced CHF by limiting the renal actions of increased endogenous ANF.     

Increased reabsorptive capacity after ureteral obstruction reduces the ability of glucose to inhibit phosphate reabsorption in rat kidney

BACKGROUND: Proximal tubular reabsorption of glucose (G), phosphate (Pi) and amino acids is energized by the transmembrane Na+ gradient, which explains why decreased concentration of one solute can enhance the transport of another. Accordingly, we postulated that the consistent increase in Pi reabsorption seen in the post-obstructed kidney (POK) could be caused, in part, by the low filtered load of glucose and reversed by glucose loading. METHODS: Renal function was examined before and after i.v. glucose loading in POKs (after release of 24 h of unilateral ureteral obstruction) and control kidneys (CK) of 10 adult rats. Brush-border membrane vesicle (BBMV) transports of Pi and glucose were assessed in POKs and CKs. RESULTS: In POKs GFR, urine flow and Na+ excretion were significantly reduced and tubular reabsorption of both Pi (T(P)/GFR) and glucose (TG/GFR) were significantly increased: T(P)/GFR, 2.0 +/- 0.2 vs 1.36 +/- 0.1; TmG/GFR, 23.4 +/- 1.7 vs 18.9 +/- 1.1 mmol/l. Glucose loading inhibited T(P)/GFR only in the CK. Initial Na+ gradient-dependent uptakes of D-glucose and Pi were similar in BBMVs from POK and CK. CONCLUSIONS: The increases in T(P)/GFR and TG/GFR seen in the POK do not result from decreased glucose delivery or from alterations in BBM Pi and glucose transporters. The reduced ability of glucose to inhibit Pi reabsorption in the POK results primarily from a generalized increase in proximal tubular reabsorption of Na+ and cotransported Pi and glucose. A specific rise in distal Pi transport capacity may be an additional adaptive response to the low filtered load of Pi in the POK. In addition, absent distal glucose reabsorption may further facilitate Pi reclamation at these sites.     

Cardiorespiratory and renal responses to arterial chemoreceptor stimulation by hypoxia or almitrine in men

1. The cardiorespiratory and renal responses to 3 h of normobaric whole-body hypoxic hypoxia (FiO2 = 0.12) as well as to arterial chemoreceptor stimulation by the oral administration of 100 mg almitrine bismesylate during normoxia were measured in 12 normotensive young men undergoing water diuresis. A third series of responses obtained under comparable conditions in the same subjects served as time controls. 2. No significant changes could be detected over time in the parameters measured in control experiments. The subjects reacted to both whole-body hypoxic hypoxia and to pharmacological chemoreceptor stimulation with significant increases in heart rate, tidal volume, minute ventilation and filtration-fraction. Overall renal vascular resistance rose significantly in hypoxia; increases in renal vascular resistance in almitrine experiments were not significant. 3. Renal fractional lithium excretion decreased significantly in response to whole-body hypoxic hypoxia and increased slightly in response to almitrine. Fractional urine and sodium excretion showed negligible changes. 4. The data indicate that, in humans, both almitrine and whole-body hypoxic hypoxia affect not only alveolar ventilation but also renal haemodynamics. 5. The renal electrolyte excretion pattern suggests that under certain circumstances (e.g. dilated renal vascular bed) acute, but well-tolerated, whole-body hypoxic hypoxia can simultaneously stimulate renal proximal tubular sodium reabsorption and inhibit distal tubular sodium reabsorption. The renal tubular responses also indicate that almitrine may influence renal tubular lithium reabsorption by, thus far, unknown mechanisms.     

Renal sodium reabsorption following induction of recovery from volume expansion

In the rat, infusion of a volume of isotonic saline equal to 2% of body weight resulted in an 82% increase in delivery of filtrate out of the proximal tubule but little or, in some animals, no change in the urinary excretion of sodium. By contrast, further degrees of volume expansion resulted in lesser increases in the distal delivery of filtrate, but were associated with a marked increase in the urinary excretion of sodium. Sixty minutes following completion of volume expansion, while the animals were still in positive sosium balance, the urinary excretion of sodium decreased 52% compared to a decrease of only 24% in the distal delivery of filtrate. During the course of progressive volume expansion and during the recovery phase, there was a dissociation between alterations in sodium reabosrption in the proximal convoluted tubule and in the whole kidney. These studies indicate that although the proximal tubule is more sensitive to changes in the extracellular fluid volume, distal nephron sites are ultimately responsible both for the natriuresis of volume expansion and the relative antinatriuresis of the recovery periods.     

Reduced renal sodium excretion in primary hypertensive patients after an oral glucose load

This study was designed to determine urinary sodium excretion in response to an oral glucose load in hypertensive patients. Fifteen hypertensive patients and eighteen normotensive subjects were studied after an overnight fast and for 4 h after the ingestion of 100 g glucose. A subgroup of untreated, nonobese, primary hypertensive patients (five of the 15 hypertensive patients) became hyperinsulinemic (total area under the insulin curve [TAUC]: 33,080 +/- 3348 microU ml(-1) 120 min-1) in response to an oral glucose load compared to normotensive subjects (TAUC: 3670 < 13.731 < 23,693 microU ml(-1) 120 min-1) or to be other subgroup of normoinsulinemic hypertensive individuals TAUC: 10,221 +/- 1615 microU ml-1 120 min-1) despite a similar serum glucose concentration in both groups. A significant decrease in renal sodium excretion in the entire hypertensive group (47.1 +/- 4.7%, P < 0.019) compared to the normotensive (20.0 +/- 10.5%) subjects was also observed during the oral glucose tolerance test. Decreased renal sodium excretion was followed by a transient increase in urinary acid excretion. We speculate that the increase in insulin secretion may be responsible for the sodium-dependent increase in intracellular Ca2+, cellular H+ output and blood pressure in a subgroup of salt-sensitive patients with hypertension. New studies should be designed to identify the precise mechanisms involved in the interaction between hypertension, serum insulin-glucose levels and the magnitude of the renal tubule reabsorption abnormality.     

Mechanism of NaCl and water reabsorption in the proximal convoluted tubule of rat kidney

The role of chloride concentration gradients in proximal NaCl and water reabsorption was examined in superficial proximal tubules of the rat by using perfusion and collection techniques. Reabsorptive rates (Jv), chloride concentrations, and transtubular potential difference were measured during perfusion with solutions (A) simulating an ultrafiltrate of plasma; (B) similar to (A) except that 20 meq/liter bicarbonate was replaced with acetate; (C) resembling late proximal fluid (glucose, amino acid, acetate-free, low bicarbonate, and high chloride); and (D) in which glucose and amino acids were replaced with raffinose and bicarbonate was partially replaced by poorly reabsorbable anions (cyclamate,sulfate, and methyl sulfate). In tubules perfused with solutions A and B, Jv were 2.17 and 2.7 nl mm-1 min-1 and chloride concentrations were 131.5 +/- 3.1 and 135 +/- 395 meq/liter, respectively, indicating that reabsorption is qualitatively similar to free-flow conditions and that acetate adequately replaces bicarbonate. With solution C, Jv was 2.10 nl mm-1 min-1 and potential difference was +1.5 +/- 0.2 mV, indicating that the combined presence of glucose, alanine, acetate, and bicarbonate per se is not an absolute requirement. Fluid reabsorption was virtually abolished when tubules were perfused with D solutions; Jv was not significantly different from zero despite sodium and chloride concentrations similar to plasma; chloride concentration was 110.8 +/- 0.2 meq/liter and potential difference was -0.98 mV indicating that chloride was close to electrochemical equilibrium. These results suggest the importance of the chloride gradient to proximal tubule reabsorption in regions where actively reabsorbable solutes (glucose, alanine, acetate, and bicarbonate) are lacking and provide further evidence for a passive model of NaCl and water transport.     

Effect of furosemide on the transport of organic substances in the kidneys

The influence of furosemide on the maximal glucose reabsorption, cardiotrast secretion and urate excretion was studied in chronic experiment. Single injection of furosemide increased the maximal glucose reabsorption in dogs. Thesere was no alteration in the secretory cardiotrast transport in response to the drug administration. Furosemide administration produced an uricosuric action in dogs and rats.     

Acute glucosuria after continuous glucocorticoid loading in the rat in vivo

We investigated the effects of the continuous infusion of various steroids in rats on renal tubular reabsorption of glucose in vivo to elucidate the pathogenesis of steroid-induced glucosuria. Urinary glucose excretion increased 60 min after administration of dexamethasone (2.38 mM). By 120 min, urinary excretion of glucose was three times higher in the dexamethasone group than in the control group (24.1 +/- 4.6 versus 72.4 +/- 16.7 micromol); the plasma level of glucose did not increase. Dexamethasone had no effect on the resorption of 1,5-anhydro-D-glucitol, which is a glucose-resembling polyol that is actively absorbed by the renal tubules as glucose. Neither estradiol nor progesterone increased urinary excretion of glucose. These findings suggest that continuous administration of a high-dose glucocorticoid selectively influences the glucose reabsorption system in the kidney.     

Renal excretion of urate in mongrel and Dalmatian dogs: a micropuncture study

Free-low micropunction experiments were performed in mongrel dogs and in Dalmatian coach hounds infused with urate to obtain Purate levels of 0.15-0.21 mM before and during the infusion of pyrazinioc acid (PZA). In the absence of PZA, mongrel dogs excreted approximately 50% and Dalmatians 140% of filtered loads of urate. In mongrel dogs net reabsorption occurred only in the proximal convoluted tubules. PZA enhanced net proximal reabsorption and revealed the occurrence of proximal secretion, whereas fractional urate excretion in the urine decreased only slightly. In Dalmation dogs urate fluxes across walls of proximal convoluted tubules resulted in either net reabsorption or net secretion, with no mean change. Net urate secretion occurred between superficial late-proximal and early-distal tubules, and considerably decreased fractional excretion of urate. The renal handling of PZA was similar in mongrel and in Dalmatian dogs.     

Haemodynamics and body fluid volumes in response to fluid loading in conscious dogs: non-excretory renal influences

1. Twelve conscious, chronically instrumented dogs were subjected to rapid loading with sodium chloride solution (150 mmol/1; saline) before and 1 day after bilateral nephrectomy (six dogs) or ureterocaval anastomosis (six dogs). Measurements were performed up to 3 h after the fluid load and included cardiac output with an electromagnetic flowmeter, mean arterial pressure and right atrial pressure with chronically implanted catheters, interstitial fluid pressure with a plastic capsule, heart rate, extracellular fluid volume, erythrocyte volume, plasma volume, plasma protein concentration and other variables. 2. The increase in cardiac output in response to saline load was significantly prolonged in the anephric dogs compared with those with uretero-caval anastomosis; mean arterial pressure, right atrial pressure and heart-rate changes were similar in both groups. 3. Plasma volume appeared to increase more in the anephric dogs than in those with uretero-caval anastomosis during the first hour after the infusion, although conflicting results were obtained with different estimates of plasma volume changes. Interstitial fluid pressure increased significantly less in the anephric dogs in the early stages of the fluid load. 4. Effective vascular compliance (the ratio of the change in blood volume to the change in right atrial pressure) appeared increased in the anephric dogs. On the other hand, the change in cardiac output for a given change in right atrial pressure was found to increase after bilateral nephrectomy. 5. It is suggested that the prolonged increase in cardiac output observed in anephric dogs was not the consequence of preferential plasma volume expansion nor of decreased venous compliance, but may reflect an alteration in the cardiac function curve.     

Renal nerves are not involved in sodium and water retention during mechanical ventilation in awake dogs

BACKGROUND: The role of renal nerves during positive end-expiratory pressure ventilation (PEEP) has only been investigated in surgically stressed, anesthetized, unilaterally denervated dogs. Anesthesia, sedation, and surgical stress, however, decrease urine volume and sodium excretion and increase renal sympathetic nerve activity independent of PEEP. This study investigated in awake dogs the participation of renal nerves in mediating volume and water retention during PEEP. METHODS: Eight tracheotomized, trained, awake dogs were used. The protocol consisted of 60 min of spontaneous breathing at a continuous positive airway pressure of 4 cm H2O, followed by 120 min of controlled mechanical ventilation with a mean PEEP of 15-17 cm H2O (PEEP), and 60 min of continuous positive airway pressure. Two protocols were performed on intact dogs, in which volume expansion had (hypervolemic; electrolyte solution, 0.5 ml x kg(-1) x min(-1)) and had not (normovolemic) been instituted. This was repeated on the same dogs 2 or 3 weeks after bilateral renal denervation. RESULTS: Hypervolemic dogs excreted more sodium and water than did normovolemic dogs. There was no difference between intact and renal-denervated dogs. Arterial pressure did not decrease when continuous positive airway pressure was switched to PEEP. Plasma renin activity, aldosterone, and antidiuretic hormone concentrations were greater in normovolemic dogs. The PEEP increased aldosterone and antidiuretic hormone concentrations only in normovolemic dogs. CONCLUSIONS: In conscious dogs, renal nerves have no appreciable contribution to sodium and water retention during PEEP. Retention in normovolemic dogs seems to be primarily caused by an activation of the renin-angiotensin system and an increase in the antidiuretic hormone. Excretion rates depended on the volume status of the dogs.     

Estrogen effects on the renal handling of calcium in the ovariectomized perfused rat

Estrogen deficiency is a major cause of bone loss in women but the mechanism is unclear. The ovariectomized (OVX) rat is a well recognized model for post-menopausal osteoporosis. In this study we have examined the effects of OVX and estrogen replacement in the OVX rat on the renal handling of calcium in response to alterations in the calcium load in the perfused rat. The interaction of estrogen administration and parathyroid hormone (PTH) was also examined in the OVX, parathyroidectomized (PTX) rat. Calcium or EDTA was infused into sham or OVX rats to obtain a range of filtered calcium loads. The excretion of calcium, was compared to the filtered load for the data from both perfusions indicating a lower calcium (P = 0.006) and sodium (P = 0.009) excretion in the OVX rat. A similar result was seen in the OVX rat replaced with 20 micrograms of estrogen valerate 48 and 24 hours prior to perfusion with calcium excretion being greater with estrogen administration (P = 0.005) compared to vehicle alone. This was not observed in the parathyroidectomized rat. Correlations between sodium and water reabsorption and calcium and sodium reabsorption during perfusion indicate that the results of OVX were due primarily to proximal tubule effects. Prior to the perfusion experiment PTH (sham vs. OVX pmol/liter, mean +/- SD; 20 +/- 6 vs. 18 +/- 4) and calcitriol (128 +/- 85 vs. 97 +/- 74) were similar in both groups, indicating that the results were not dependent on calcitropic hormone effects. It is concluded that, in the perfused rat, OVX results in decreased excretion of calcium and sodium as a result of estrogen effects on the renal proximal tubule, an effect dependent on PTH. This effect is opposite to that found in postmenopausal women, perhaps due to the high filtered load of calcium used in the experimental design and species differences in the relative importance of proximal versus distal calcium handling.     

Renal adaptation to dietary sodium restriction in moderate renal failure resulting from chronic glomerular disease

The renal response to sodium restriction was evaluated, and the concurrent changes of the plasma levels of aldosterone (ALDO) and atrial natriuretic peptide (ANP), in healthy patients (NOR), in normotensive patients with non-nephrotic chronic glomerulonephritis and normal renal function (GN), and in patients with glomerulonephritis and moderate renal failure (GFR, 41 +/- 4 mL/min; CRF). The three groups were studied for 1 wk after changing from a normal-sodium diet (NSD, 235 mEq NaCl/day) to a low-sodium diet (LSD, 35 mEq NaCl/day). All patients reached a steady sodium balance within the 4th and 5th day of LSD with an analogous cumulative loss of sodium. After salt restriction, the fractional urinary sodium excretion diminished by the same extent in the three groups, whereas the fractional free-water generation, measured during water diuresis, did not vary in NOR and markedly decreased in GN and CRF. Plasma levels of ALDO were similar in all groups at NSD and similarly increased during LSD. In GN and CRF, as compared to NOR, ANP levels were higher at NSD and decreased by a minor extent during LSD. Notably, in GN and CRF, but not in NOR, the attainment of the new sodium balance after sodium restriction was preceded by a significant parallel reduction of blood pressure and GFR; the GFR decline was secondary to a major decrement of RPF so that filtration fraction (FF) increased. It was concluded that in NOR, distal tubular effects of ANP and ALDO account for the attainment of sodium balance during LSD. As a difference, both GN and CRF patients achieve the new sodium balance primarily through hemodynamic changes: the renal hypoperfusion secondary to a decrease in blood pressure that diminishes the filtered load of sodium, and the increase of FF that enhances the proximal tubular sodium reabsorption. This abnormal response seems related to both the minor suppression of ANP and the increased salt-sensitivity of blood pressure that are likely the result of the presence of volume expansion.     

Effect of acute increases in filtered HCO3- on renal hydrogen transporters: II. H(+)-ATPase

Adaptive increases in renal bicarbonate reabsorption occur in response to acute increases in filtered bicarbonate (FLHCO3). In a previous study, we showed that an increase in FLHCO3 induced by plasma volume expansion increased the Vmax for Na+/H+ exchange activity in renal cortical brush border membrane vesicles (BBMV), providing a potential mechanism for the adaptive increase in HCO3- reabsorption. The present studies were undertaken to determine whether the increase in FLHCO3 induced by plasma expansion also stimulates the other major H+ transporter in cortical BBMV, the H(+)-ATPase. H(+)-ATPase activity was assessed in BBMV obtained from hydropenic and plasma expanded Munich-Wistar rats, using a NADH-linked ATPase assay. H(+)-ATPase activity was measured as the ouabain and oligomycin-insensitive, bafilomycin A1-sensitive component of total ATPase activity. Acute plasma expansion doubled single nephron FLHCO3, and this change was associated with a 64% increase in the Vmax for H(+)-ATPase activity, with no change in apparent Km. The Vmax for H(+)-ATPase activity correlated directly with whole kidney GFR and FLHCO3 (r = 0.68 and 0.72, respectively), and with single nephron GFR and FLHCO3 (r = 0.76 and 0.80, respectively). Thus, the mechanism for the adaptive increase in proximal tubular HCO3- reabsorption that occurs in response to acute increases in FLHCO3 appears to be related to increased activity of both H(+)-ATPase and Na+/H+ exchange in the apical membrane of the proximal tubule epithelium.