Reabsorption Of Na Research Articles

Renal handling of cadmium in perfused rat kidney and effects on renal function and tissue composition.

Isolated rat kidneys perfused with a Krebs-Ringer bicarbonate (KRB) solution containing 1 microM CdCl2 plus 6% substrate-free albumin (SFA) and a mixture of substrates accumulated substantially less cadmium in tissue than kidneys perfused with 1 microM CdCl2 in a protein-free KRB solution containing the same substrates: 11 vs. 205 nmol Cd/g dry wt. Decreasing the glomerular filtration rate (GFR) by occluding the ureters of kidneys perfused in the absence of albumin did not change the rate of net tissue uptake of cadmium (Cd), suggesting that the kidney can extract Cd from the peritubular capillary fluid and that net uptake of Cd is not dependent on the reabsorption of filtered Cd. The tissue accumulation of large quantities of Cd (1.8 mumol Cd/g dry wt), which established levels of non-metallothionein-bound Cd exceeding 1 mumol Cd/g dry wt, caused no changes in either GFR, perfusion flow rate, fractional reabsorption of Na+, fractional reabsorption of K+, fractional reabsorption of glucose, or free-water clearance. However, discrete changes in renal tissue K+ content were observed. Exposure to 1 microM CdCl2 resulted in a net loss of renal tissue K+ in rat kidneys perfused with substrate-enriched KRB containing 6% albumin. Exposure to 0.8 microM or 7 microM CdCl2 completely prevented K+ loss from kidneys perfused with a substrate-enriched, protein-free KRB solution.

Renal function in sea snakes. II. Sodium, potassium, and magnesium excretion.

Renal clearance studies performed on the sea snake Aipysurus laevis demonstrated net tubular reabsorption of Na and both net tubular secretion and reabsorption of Mg and K. Fractional excretion of Na (FENa) was 0.05 under control conditions and increased markedly with hyperosmotic salt loading. Within each group, however, higher glomerular filtration rates were accompanied by disproportionately greater Na reabsorption. FEMg was 0.66 under control conditions and increased with Mg loading. The rate of Mg secretion was positively correlated with the urine flow rate. However, Mg loading caused a flow-independent increase in Mg secretion that was correlated with increasing plasma Mg concentration. FEK was 0.86 under control conditions and increased with K loading as a result of enhanced K secretion by the renal tubules. Like renal Mg secretion, renal K secretion showed a flow-dependent component as well as a flow-independent component related to plasma K concentration.

L'échangeur Na +/H + des cellules eucaryotes : Propriétés biochimiques et pharmacologiques, rôle physiologique

A membrane mechanism that catalyses the electroneutral exchange of Na+ for H+ has recently been characterized in a variety of eukaryotic cells. This exchanger is inhibited by amiloride, a potent diuretic drug. It has been implicated in a number of important physiological processes such as the regulation of the intracellular pH, the reabsorption of Na+ by the renal proximal tubule, the regulation of the cell volume and the fertilization of the sea urchin egg. The Na+/H+ exchanger seems able to mediate the action of growth factors. The biochemical and pharmacological properties of the Na+/H+ exchange system are reviewed. They are very similar in the different cell types that have been studied. Yet the Na+/H+ exchange system can fulfil different functions in different cell types depending i) on its properties of interaction with intracellular H+, ii) on the presence of other membrane structures that are involved in the maintenance of transmembrane Na+ and H+ gradients and iii) on the presence of extracellular messages that modify its catalytic properties and, among them, its interaction with internal H+.

Tubular reabsorption in normal renal function.

The purpose here is to examine in relation to normal renal function three factors which might affect tubular reabsorption: (1) The reabsorption of SO4, PO4, K, Cl, HCO3 and water are all linked to the reabsorption of Na. This would amount to the reabsorption by the tubules of a net reabsorbate of a composition similar to Locke's fluid. Fixed linkage of the reabsorption of a substance to the reabsorption of Na would be a very effective way of maintaining its plasma concentration within a narrow range. The substance would be retained unless its plasma concentration exceeds a threshold value and then small increase in plasma concentration determines its excretion. (2) The rate of reabsorption of Na and substances linked to it is increased when the volume of the intraluminal fluid is increased. This would explain why there is only a small increase in the excretion of Na and other electrolytes when glomerular filtration rate is increased after a meal of meat. (3) Plasma protein concentration affects tubular reabsorption. This would explain why fall in plasma protein is a main agent determining Na excretion in normal animals. Trying to see 'how far the observed facts can be brought into accord with a theory' reveals the difficulty of applying critical tests. On the one hand, the theories are not stated quantitatively in reference to the small changes of normal life; rather the evidence is from experiments with large changes. On the other hand, the small changes within the range of normal function, while themselves statistically significant, are too small for effective investigation of circumstances which may modify them. In the examples discussed here, we cannot say more than that the theories could explain the facts and their participation cannot be excluded.

Stimulation by antidiuretic hormone of electrolyte tubular reabsorption in rat kidney.

The effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on renal excretion and tubular transport of water and electrolytes were investigated in homozygous DI Brattleboro rats. To ascertain these effects on the loop of Henle, circulating glucagon, parathyroid hormone, and thyrocalcitonin were reduced before the experiments, as these hormones are believed to stimulate the same cells of the thick ascending limb as ADH. dDAVP did not alter either glomerular or proximal tubular functions. In the loop, it consistently raised reabsorption of Mg, Ca, K, and, to a lesser extent, Na and Cl, but phosphate transport was not affected. dDAVP lowered the urinary excretion rates for Mg, Ca, K, Cl, and total solutes. For Mg, this reduction was independent of the drop in the urinary flow rate following dDAVP administration but was significantly correlated to this drop in the case of Ca, K, Cl, and total solutes. Na and P excretions were not altered by dDAVP. It is concluded that, in vivo, administration of ADH 1) stimulates reabsorption of Na, Cl, Mg, Ca, and K by the thick ascending limb, 2) consistently enhances Mg reabsorption by the whole kidney by enhancing reabsorption in the loop of Henle, and 3) at maximal antidiuresis, raises Ca, K, Cl, and total solute reabsorption, probably because of the drop in tubular flow rates in the distal parts of the nephron consequent to the hormone administration.

Intracellular microelectrode characterization of the rabbit cortical collecting duct

Cortical collecting ducts of the rabbit were perfused in vitro and the intracellular potential (Vbl) was measured with KCl-filled microelectrodes. The ratio of apical to basolateral membrane resistance (Ra/Rbl) was estimated from the voltage divider ratio using cable analysis. In control tubules Vbl averaged--84.0 +/- 2.5 mV and Ra/Rbl was 0.83 +/- 0.11. Pretreatment of the rabbits with mineralocorticoid caused Vbl to hyperpolarize to--105.8 +/- 3.1 mV and Ra/Rbl to decrease slightly to 0.62 +/- 0.10. A 10-fold increase of the luminal [K+] caused a 40.6 +/- 3.1 mV depolarization of Vbl in control tubules and a 33.0 +/- 4.2 mV depolarization in tubules from DOCA-pretreated rabbits. Concurrently, Ra/Rbl decreased in both groups, consistent with the existence of a conductive K+ channel at the apical cell membrane. This apical K+ channel was not sensitive to amiloride but was blocked by Ba2+. Conductive movement of Na+ across the apical membrane was also apparent in that Ra/Rbl increased with amiloride from 0.61 +/- 0.10 to 1.45 +/- 0.28. A 10-fold increase in the bath [K+] caused a 28.6 +/- 3.8 and a 49.4 +/- 4.4 mV depolarization of Vbl in tubules obtained from control and DOCA-pretreated rabbits, respectively. In both groups Ra/Rbl increased, suggesting that the basolateral cell membrane also contains a conductive K+ channel. Taken together the results support a model in which the transepithelial reabsorption of Na+ and the transepithelial secretion of K+ are driven by the Na+-K+-ATPase located in the basolateral cell membrane, with passive movement of these ions occurring through separate conductive pathways in the apical cell membrane.

Molecular actions of diuretics.

The criteria upon which diuretics are classified is based upon their site of action within the nephron. Carboanhydrase inhibitors act in the proximal tubule, high-ceiling diuretics in the ascending loop of Henle, the thiazides in the early distal tubule and the potassium-sparing diuretics in the late distal tubule and in the collecting duct. On the molecular level diuretics do not inhibit Na+-K+-ATPase but interfere with the permeability of the tubule membranes or transport systems for certain ions and thus also influence the potential differences in the different parts of the nephron. Since carboanhydrase is located in the proximal tubule cells, not only in the cytosol but also in the brushborders and in the peritubular membranes, acetazolamide and other carboanhydrase inhibitors act on three different sites in these cells. The loop diuretics inhibit the secondary active chloride reabsorption. The receptors in this part of the nephron are stereospecific. Only the levorotatory isomere of ozolinone has active diuretic properties whereas the dextrorotatory isomere does not. Perfusion experiments of the loop of Henle with different lectins give evidence that glycoproteins containing alpha-1-fucose are involved in the reabsorption of Na+ and Cl-. Experiments on the isolated stripped rabbit colon under the condition of chloride secretion reveal striking similarities between the receptors for chloride reabsorption in the luminal cell membranes of the ascending loop of Henle and in the serosal cell membranes of the colon. The potassium-sparing diuretics amiloride and triamterene act by blocking sodium channels in the distal parts of the nephron. Thus the lumen negative potential difference decreases and (passive) potassium secretion is diminished.

Increased Na+-H+ exchange in brush border vesicles from dogs with renal failure.

In the remnant kidney model of chronic renal failure, absolute reabsorption of Na+ in the proximal tubule of the remaining nephrons is increased over normal. Absolute proximal tubular reabsorption of bicarbonate and proximal tubular H+ excretion per nephron have also been shown to be increased over normal in his model of renal disease. Na+ uptake in membrane vesicles isolated from the brush border membrane of remnant kidneys of dogs with chronic renal failure is increased over uptake in membrane vesicles isolated from kidneys of normal dogs. In the present studies an amiloride-sensitive, electroneutral Na+-H+ exchanger was identified in canine renal brush border membrane vesicles. Na+ uptake in membrane vesicles in the presence of an initial H+ gradient (intravesicular pH less than extravesicular pH) was increased in membrane vesicles isolated from the remnant kidneys of dogs with chronic renal failure over that in membrane vesicles from kidneys of normal dogs. This increase was abolished by amiloride. It is possible that the alterations in Na+ and bicarbonate reabsorption and H+ excretion in the remnant kidney model of chronic renal failure can be explained on the basis of increased activity of the Na+-H+ exchanger in the renal brush border membrane.

ADH-PGE2 interactions in cortical collecting tubule. I. Depression of sodium transport.

Antidiuretic hormone (ADH) (200 microunits/ml Pitressin or synthetic arginine vasopressin) causes a transitory increase followed by a sustained decrease in the potential difference (PD) and in the net fluxes of sodium and chloride across rabbit cortical collecting tubules perfused in vitro. The inhibitory action of vasopressin is reversible; removal of the hormone from the bath promotes recovery in the PD and in the transport of sodium and chloride to the level of the controls. After 70 min of incubation with ADH, 10(-5) M meclofenamate, an inhibitor of the synthesis of prostaglandins, was added to the bath of some tubules. Despite the presence of ADH, the PD and ionic fluxes increased to control levels. The introduction of exogenous prostaglandin E2 (10(-5) M PGE2) to the bathing medium containing ADH and meclofenamate mimicked the inhibitory action of ADH, decreasing the PD and the reabsorption of sodium and chloride. Pretreatment of collecting tubules with meclofenamate prevented the inhibitory effect of ADH. These findings show that vasopressin exerts a prolonged inhibitory action on PD and on net reabsorption of Na and Cl and that this action may be exerted through stimulating the biosynthesis of prostaglandin E2 by the cortical collecting tubule.

Antihypertensive effect of riboflavin analogs in rats with mineralocorticoid-induced hypertension.

This study investigated whether the riboflavin analogs, 7,8-dimethyl-10-formylmethyl isoalloxazine (FMI) and 7,8-dimethyl-10-(2'-hydroxyethyl) isoalloxazine (HEI), are effective antihypertensive agents in mineralocorticoid-induced or deoxycorticosterone acetate (DOCA)-salt hypertension. These studies are based on our previous observation tht aldosterone enhances the biosynthesis of renal flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) from riboflavin, and that FMI and HEI competitively inhibit conversion of riboflavin to FMN and reabsorption of Na+ in the kidney of adrenalectomized rats. When 1.6 mg of FMI or HEI were administered simultaneously with 3.0 mg of DOCA, the tail systolic blood pressure (SBP) of unanesthetized rats rose only to 136 +/- 5 mm Hg (standard error of the mean, SEM) compared to 163 +/- 5 mm Hg during DOCA therapy alone (p less than 0.0005). This hypotensive effect of FMI or HEI was noted after the fourth week of treatment and persisted through the ninth week. The rats tolerated the medication well and had no signs of riboflavin deficiency. DOCA administration alone resulted in a 24% increase in iliopsoas muscle Na+ concentration (p less than 0.0005), and a 0.8% increase in the water content of the muscle (p less than 0.025), suggesting a positive Na+ balance. Administration of FMI or HEI blunted the ability of DOCA to increase muscle Na+ concentration (p less than 0.025), water content (p less than 0.01). HEI treatment of the Kyoto strain of spontaneously hypertensive rats (SHR) did not lower their mean SBP. Thus it appears that the hypotensive actions of FMI or HEI are closely associated with their ability to modify the effects of mineralocorticoids on NA+ balance.

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.

Ion transport by the urinary bladder of the gobiid teleost, Gillichthys mirabilis.

Transport characteristics of the two epithelial cell types lining the urinary bladder of the goby can be studied in Ussing-type chambers. Cuboidal cell regions from seawater- and 5% seawater-acclimated fish exhibit little mucosal-to-serosal Na or Cl transport. In contrast, columnar cell regions from both seawater- and 5% seawater-acclimated fish transport substantial amounts of Na and Cl. Whereas all electrolyte transport in 5% seawater-acclimated fish is electrically silent (neutral), columnar cell regions from seawater-acclimated fish possess an electrogenic Na transport component in addition to the neutral transport. Columnar cell regions also possess a Cl/Cl exchange diffusion mechanism. Neutral Na and Cl transport are not altered in response to external salinity; electrogenic transport varies both with acclimation to salinity and season. Reabsorption of Na and Cl from urine reduces excretory losses of these ions from 5% seawater-acclimated fish and drives urinary bladder water reabsorption in seawater-acclimated fish.

Low GFR in the early postnatal period is to a large extent due to low renal plasma flow (RPF)

Since the low RPF appears to be due mainly to active vaso-constriction, the question is raised whether renal vaso-constriction is needed to minimize the energy demands of the kidney in early postnatal life. The work load to the kidney is determined by the GFR. The most energy demanding process of the kidney is reabsorption of Na (TNa). In the present study the relationship between TNa and 02 consumption are compared in the immature kidney of 24 days old rats (R24) and the mature kidney of 45 days old rats (R 45). Determinations are made of filtered Na (FNa), TNa and 02 consumption by extraction and clearance techniques during hyeropenia (HP) and volume expansion (VE). The two conditions are chosen since VE will cause vaso-dilatation of the immature kidney. This finding was confirmed in the present study and resulted (see table) in a marked increase of TNa in volume expanded R24.Yet the increase in 02 consumption during the transition from HP to VE was less pronounced in R24 than in R45. In volume expanded R24 the amount of TNa/μmol oxygen consumed (Na-02) increased significantly. This suggests that in the volume expanded R24 the increased tubular load of sodium is reabsorbed by non oxidative pathways, either passive or anaerobic.

Bicarbonate and chloride transport in relation to the acidification or alkalinization of the urine.

Although the electrogenicity of the active reabsorption of sodium and bicarbonate (or secretion of protons) has been well-established in the short-circuited turtle bladder preparation, the nature of the active reabsorption of chloride and secretion of bicarbonate has been controversial. These processes have been ascribed to the separate actions of two discrete electrogenic pumps or to the single action of a metabolically driven electroneutral anion exchange mechanism. The present report deals with these transport processes per se; with the relations among serosal bicarbonate,glucose, and the reabsorption of Na and Cl; and finally with the application of the Heinz model for inversion of an active transport as a tentative single mechanism for the alkalinization and acidification of the urine.

Ion and water transport by isolated cockroach salivary glands.

When the isolated salivary glands of the cockroach Nauphoeta cinerea Oliver are stimulated by dopamine, the putative neurotransmitter, they secrete a fluid containing (mM):Na, 121; K, 47; Cl, 143. Stimulation of glands by 5-hydroxytryptamine or the neuro-transmitter evokes a secretion identical in Na composition to this. Dopamine-evoked secretion is abolished in the absence of extracellular Na. The relationship between the rates of fluid secretion and Na transport is linear. However, at very low rates of secretion the Na concentration falls. Calcium, K and Cl ions can be removed from the bathing solution without abolishing fluid secretion. Our evidence suggests that (i) the primary secretion is formed by active transport of Na in the acini, and (ii) the ionic composition of this secretion is modified by re-absorption of Na and an independent secretion of K in the ducts.

The effects of a disulphonic stilbene on chloride and bicarbonate transport in the turtle bladder.

1. In turtle bladders bathed by Na-free media containing Cl and HCO3, the mucosa is electropositive to the serosa. Serosally applied 4-acetamido-4'-isothiocyano-2,2'-disulphonic stilbene (SITS) reduces the p.d. and Isc by 100%, and reduces the rate of net Cl reabsorption in some bladders but not in others. 2. In the absence of exogenous HCO2 (Cl present), SITS reduces the p.d. and Isc by 100%, and reduces the rate of mucosal acidification by 80%; net Cl reabsorption is not detectable under these HCO3-free bathing conditions. 3. In the absence of exogenous Cl (HCO3, present), the mucosa is also electropositive to the serosa and serosally applied SITS reverses the orientation of the p.d. and Isc so that the mucosa becomes electronegative to the serosa. 4. This constitutes sufficient evidence for the active, electrogenic secretion of an anion, probably HCO3. These data are explained by an analogue of discrete, electrogenic pumps and paths for the reabsorption of Na, Cl, and HCO3, and the secretion of HCO3.

Correction of metabolic acidosis by the kidney during isometric expansion of extracellular fluid volume.

In dogs with chronic hypochloremic metabolic alkalosis associated with ECFV contraction, plasma [HCO-3] ([HCO-3]p) normalizes during expansion of ECFV with a solution containing Cl- and HCO-3 in concentrations duplicating those in the plasma before expansion (isometric expansion). The kidney selectively rejects administered HCO-3 and retains Cl-. If this preferential Cl- less than HCO-3 reabsorptive selectivity were a characteristic renal response to ECFV expansion, isometric expansion during hyperchloremic acidosis would exacerbate the acid-base disturbance rather than correct it as it does in alkalosis. We examined the effect of isometric expansion in dogs with chronic hyperchloremic metabolic acidosis induced by HCl feeding or mineralocorticoid hormone deficiency. During expansion, as the expected decrease occurred in the fractional reabsorption of Na+, a lesser decrease occurred in fractional reabsorption of HCO-3, whereas a greater decrease occurred in fractional reabsorption of Cl-. The kidney selectively retained administered HCO3 and rejected Cl-. [HCO-3]p normalized. The shift to bicarbonate-selective from chloride-selective anion reabsorption during ECFV expansion in metabolic acidosis vs. metabolic alkalosis indicates that in response to ECFV expansion- the kidney selectively alters the ratio of bicarbonate to chloride concentration in the tubular reabsorbate in the direction that tends to normalize plasma acid-base composition, irrespective of the direction of deviation of the initial plasma bicarbonate concentration. The signal that initiates the shift in anion reabsorptive selectivity remains to be identified.

Acute compensatory adaptation of renal function following contralateral kidney exclusion in Brattleboro rats with diabetes insipidus.

1. The function of the remaining kidney following ligation of a single renal pedicle in anaesthetized rats with hereditary hypothalamic diabetes insipidus (DI) was studied using clearance methods. Values were compared with those obtained in DI rats which had been sham operated. 2. A small increase in the glomerular filtration rate of the remaining kidney was observed, which was statistically significant after 150 min. Increases in effective renal plasma flow were also observed, but these were not statistically significant. 3. The fractional excretion rates of Na and K increased immediately after contralateral kidney ligation; as a result total Na and K excretion rates remained similar to values in sham operated animals with both kidneys intact. 4. Fractional urine flow (V/GFR) increased by approximately 40% after contralateral ligation. It is argued that, since water reabsorption in the diluting segments of the nephron was unlikely to have been reduced, the increase in V/GFR was an indication that fractional fluid reabsorption in the proximal nephron had been inhibited. 5. Clearance determinations showed that the fractional reabsorption of Na in the proximal nephron was similarly reduced after contralateral ligation. However, Na reabsorption in the distal nephron increased, though not by enough to prevent a doubling of fractional sodium excretion. 6. The osmolalities of interstitial fluids obtained from the medulla and papilla of the contralateral kidney 2 hr after unilateral renal pedicle ligation were slightly, but significantly, higher than corresponding values in sham operated rats. This raises the possibility that salt reabsorption in the ascending limb of Henle might be enhanced immediately after contralateral renal exclusion.

Effect of Cholera Toxin on Renal Tubular Reabsorption of Glucose and Bicarbonate

SummaryCholera toxin (CT) reduces tubular reabsorption of Na, Cl, Ca, Mg and P most probably through stimulation of a renal adenylate cyclase-cyclic AMP system, and it is possible that an increased production of nephrogenous cyclic AMP during extracellular fluid volume expansion may be partly responsible for the observed natriuresis. In order to further evaluate the role of renal cyclic AMP in renal tubular transport, we studied the effect of CT on glucose (TRG) and bicarbonate reabsorption (TRHCO3).During the period of maximal effect of CT on tubular transport (100-140 min of CT infusion into one renal artery) both the TRG and TRHCO3 were lower in the infused kidney than in the contralateral noninfused kidney; TRG as mg per 100 ml GFR was 254 ± 32.7 vs 363 ± 43.5 (P < .01), and TRHCO3 as mEq per 100 ml GFR was 2.09 ± 0.06 vs 2.53 ± 0.06 (P < .01). The data indicate that CT suppresses glucose and bicarbonate reabsorption together with that of sodium and as such assign to role for renal cyclic AMP in the r...

Studies on the avian shell gland during egg formation: The effect of acetazol‐amide on the transfer of ions to the albumen1

Twenty-five laying hens were fed on a diet containing 100 mg acetazolamide/kg in order to determine the effects of a decrease in the activity of carbonic anhydrase on the transfer of minerals to the egg albumen. Treatment with acetazolamide decreased the rate of shell formation by 44%; reduced the concentrations of water and Na+ in the albumen at the beginning of the plumping stage but increased the accumulation of water during plumping; increased the concentration of Cl- in the albumen after the 6-h stage without any appreciable change in K+ and Ca2+ concentrations. The computed relationships between the concentrations of different ions also showed that the transfer of water and Na+ were linked during egg formation, that a water-independent, acetazolamide-sensitive reabsorption of Na+ occurred after the 10-h stage and that Na+ and Cl- moved simultaneously up to 14 h but with the ratio of Cl- to Na+ three times higher in the treated group. It is concluded that acetazolamide impairs the transfer of Na+ and Cl- between the albumen and the extracellular fluid and that secretion of Ca2+ into the uterine lumen seems to depend on Na+ and Cl- reabsorption.