Net Sodium Flux Research Articles

Solute transport in continuous hemodialysis: A new treatment for acute renal failure

A pumpless dialysis technique which combines continuous convection and diffusion was studied in 15 critically ill acute renal failure patients. Fluid identical in composition and purity to that used in peritoneal dialysis was continuously circulated (single-pass) at 16.6 cc/min through the dialysis compartment of a 0.43 m2 flat plate PAN membrane dialyzer. Whole blood clearances for urea, creatinine and phosphate averaged 25.3 +/- 4.4 cc/min, 24.1 +/- 5.5 cc/min and 21.3 +/- 5.6 cc/min, respectively. Over the range of blood flows studied (50 to 190 cc/min) clearances of these solutes were independent of blood flow rate but rather were determined by both dialysate flow rate and ultrafiltration rate. In contrast net fluxes of calcium and sodium were correlated only with ultrafiltration rate. Bicarbonate loss was 0.52 +/- 0.11 mEq/min; K+ balance varied with dialysate K+; glucose uptake from dialysate was 107 +/- 24.0 mg/min. In fresh non-clotting dialyzers, mean ultrafiltration rate was 8.1 cc/min. At QBi of 70 to 190 cc/min, dialysate and blood solute equilibrate yielding a total clearance equal to the dialysate outflow, or 25 cc/min, that is, the sum of dialysate flow rate plus ultrafiltration rate. In comparison to currently used continuous arteriovenous hemofiltration (CAVH), the exceptionally-high solute clearances obtained with continuous hemodialysis constitute a significant improvement in continuous renal replacement therapy.

Effect of adrenalectomy on transport in the rat medullary thick ascending limb.

Previous studies in adrenalectomized (Adx) rats suggest that aldosterone may regulate ion transport in the ascending portion of Helen's loop. In order to examine directly the effect of adrenalectomy on transport, medullary thick ascending limb (Mtal) segments were isolated from Adx, Adx replaced with aldosterone (Adx + Ald, 0.5 micrograms X 100 g X body wt X d), and control Sprague-Dawley rats. Both net sodium and net chloride fluxes were significantly less in the Mtal segments from Adx rats compared with those in the control or Adx + Ald group. Physiologic levels of exogenous aldosterone increased net sodium chloride flux toward control values in the Adx + Ald group. Net potassium flux was not different among the three groups. We conclude that adrenalectomy impairs reabsorptive NaCl but not K transport in the Mtal, and that aldosterone restores this process. This reabsorptive defect may contribute to the urinary concentrating and diluting abnormality associated with adrenal insufficiency.

Short-chain fatty acid transport and its effects on ion transport by rabbit cecum.

Short-chain fatty acid (SCFA) metabolism and transport were examined in vitro across isolated rabbit cecal epithelia whose primary function is absorption of these solutes. This study shows that although there was some low-level metabolism of SCFAs to ketone bodies by the isolated cecum, a significantly higher oxygen consumption was sustained for a longer time period by tissues incubated in glucose-containing salines. The cecum supported a significant net secretory flux of acetate (J net Ac- = -1.13 +/- 0.13 mu eq X cm-2 X h-1) and propionate (J net Pr- = -0.61 +/- 0.14 mu eq X cm-2 X h-1). This study also shows that glucose significantly enhanced short-circuit current (Isc), tissue conductance (Gt), and sodium transport across this tissue. Neither Ac- nor Pr- enhanced net sodium flux (J net Ac-) but Pr- significantly reduced net chloride flux (J net Cl-), whereas Ac- had no effect. The increase in Isc and Gt observed in the presence of SCFAs was attributable to the presence of SCFA in the serosal bathing solution alone. To explain the latter finding and the unexpected finding of SCFA secretion, the existence of an electrogenic anion (HCO3-) secretory pathway is postulated. It is suggested that this system can accommodate SCFAs in vitro and that it is a Na+-dependent system located on the basolateral membrane of the cecal cell.

Epithelial responses evoked by stimulation of submucosal neurons in guinea pig distal colon.

The influence of submucosal neurons on ion transport in the guinea pig distal colon was examined in muscle-stripped sheets of submucosa-mucosa set up in Ussing flux chambers. Spontaneous variations in potential differences (PD) and short-circuit current occurred ranging from positive currents associated with luminal negative PDs to negative currents with luminal positive PDs. Basal current in both groups was reduced by mucosal amiloride. In tissues with positive or negative short-circuit currents, unidirectional mucosal-to-serosal sodium fluxes were greater than serosal-to-mucosal fluxes and small net absorptive fluxes were present. Little or no chloride secretory flux was present. Electrical stimulation of submucosal neurons evoked a tetrodotoxin-sensitive increase in short-circuit current in tissues with positive or negative short-circuit currents. This was due to an increase in net chloride flux and little change in net sodium flux or residual flux. The increase in net chloride flux was due almost entirely to an increase in serosal-to-mucosal chloride flux and was associated with an increase in total tissue conductance. The stimulus-evoked response was reduced by atropine. These results suggest that stimulation of submucosal neurons that innervate the distal colonic epithelium evokes a large chloride secretory response that is due in part to release of acetylcholine at neuro-enterocyte junctions.

Hypercapnic acidosis in the rainbow trout (Salmo gairdneri). I. Branchial ionic fluxes and blood acid–base status

Branchial solute fluxes as well as blood respiratory, ionic, and acid–base variables were monitored before, during, and after 72 h of exposure to external hypercapnia (1% CO2; [Formula: see text]). Hypercapnia induced an immediate extracellular respiratory acidosis that was gradually regulated over the 72-h period by an elevation of the plasma bicarbonate [Formula: see text] level. Red blood cell pH changed in a manner similar to whole blood pH but the reduction of red blood cell pH during hypercapnia was significantly less than that predicted from in vitro experiments. We argue that elevated plasma levels of epinephrine in the first 12 h of hypercapnia may serve to stabilize red blood cell pH during the severe reduction of whole blood pH, thereby preventing excessive depressions of arterial oxygen content. Elevated external CO2 tension caused changes in the branchial net flux (JnetCl−) such that the arithmetic difference between sodium net flux (JnetNa+) and JnetCl− (JnetNa+ – JnetCl−) increased during hypercapnia and then decreased post-hypercapnia. These results are consistent with enhanced branchial acid excretion and are discussed with reference to the involvement of the gill in the regulation of hypercapnic acidosis.

Mechanisms of transport of Na + and Cl − in the lizard colon

1. 1. Ionic fluxes of sodium and chloride across lizard colon mucosa were measured and compared with the electrical characteristics of the tissue under voltage-clamped conditions. 2. 2. In a Ringer-bicarbonate solution there was both a net sodium flux ( J net Na) and a net chloride flux ( J net cl) from mucosa to serosa. The net flux residual ( J R) was near zero, indicating that net sodium and chloride transport is the result of an electrically neutral transport mechanism. 3. 3. In the presence of sodium, the net chloride flux was abolished and the short-circuit current ( I sc ) and the electrical potential difference (PD) were unchanged. In the absence of chloride the net sodium flux was abolished and the short-circuit current and electrical potential difference were not modified. 4. 4. From an analysis of the effects of the inhibitors, furosemide, amiloride and disulfonic stilbene (DIDS), a plausible model was developed to explain the characteristics of sodium and chloride absorption.

Sodium fluxes during hemodialysis.

Three sets of experiments were performed to determine the effect of the dialysate sodium concentration on the sodium balance of patients undergoing maintenance hemodialysis. First, patients were treated with three different dialysate bath sodium concentrations: 125-132 mEq/l (n = 7), 135-140 mEq/l (n = 11) and 145-150 mEq/l (n = 6). We demonstrated that the pretreatment plasma sodium concentration was independent of the sodium concentration of the dialysate used. Second, the plasma sodium concentration available for diffusion during the treatment was calculated from the plasma sodium concentration and the plasma proteins. The accuracy of this calculation was demonstrated by comparing the predicted value with the concentration of sodium measured in an ultrafiltrate obtained at minimal filtration fraction. Third, the sodium fluxes using a hypernatremic or hyponatremic dialysate were calculated for 100 ml of plasma going through the dialyzer. At steady state, no significant differences in net sodium fluxes were demonstrated between hyper- and hyponatremic dialysis.

The effects of starvation and sexual maturation on Na + transbranchial fluxes following direct transfer from fresh water to sea-water in rainbow trout ( Salmo gairdneri)

1. 1. The perfused isolated head technique has been used to measure sodium arterial fluxes following direct transfer from fresh water to sea-water. 2. 2. A starvation-related decrease in net sodium flux is reported. 3. 3. Sexual maturation slackens the decrement of this net flux. 4. 4. In starved fish, the cytological modifications of chloride cells following such a transfer are delayed. 5. 5. This effect of starvation is discussed in terms of lamella sodium imperviousness.

Adaptations of sodium balance to low pH in a sunfish (Enneacanthus obesus) from naturally acidic waters

Net sodium flux (Jnet), sodium influx (Jin), and sodium efflux (Jout) were measured in two sunfish,Enneacanthus obesus (acid-tolerant) andLepomis gibbosus (less acid-tolerant), during 24 h exposure to soft water of pH's 4.0 and 3.5.E. obesus exhibited a mild transitory disturbance at both pH's caused by inhibitedJin and slightly stimulatedJout. Body and plasma ion concentrations ofE. obesus were measured weekly during exposures for 5 weeks to acidified artificial soft water (ASW). Body sodium concentration declined 30% during 2 weeks exposure to pH 3.5 but no further during the next three weeks. Exposure to pH 4.0 had no effect on body sodium concentration during the entire 5 weeks. Plasma sodium concentration declined 15% over a 3 week period at pH 3.5; there was no further change in the next two weeks. Plasma potassium concentrations, which were measured after 4 and 5 weeks at pH's 5.8 and 3.5 in ASW, were not significantly different. In a separate two week long experiment, plasma sodium concentration ofE. obesus in ASW was correlated with pH between pH's 3.5 and 7.5. This effect was mainly due to increases above pretreatment levels at pH 4.5 and above. Increased ambient sodium and calcium concentrations had no effect on body sodium concentration ofE. obesus at pH 5.8, but mitigated the effects of exposure to pH 3.5. Increased calcium concentrations up to 25 μM at pH 3.5 increased body sodium concentration, but higher concentrations had no additional effect. Body potassium concentration and body water concentration ofE. obesus were linearly related to body sodium concentration under a wide variety of external conditions. This suggests the presence of a mechanism by whichE. obesus regulates plasma sodium levels and body fluid compartments in response to sodium loss. In contrast toE. obesus, L. gibbosus showed larger sodium losses at low pH resulting from greater acceleration ofJout; those exposed at pH 3.5 died in less than 12 h.L. gibbosus also had reduced body and plasma sodium concentrations at pH 4.5 and below; those at pH 4.0 were the lowest. Body potassium concentration ofL. gibbosus was reduced in those fish exposed to pH 4.0 and below, but body water was increased. Thus there are striking differences in the ability to regulate ion and water balance at low pH between an acid-tolerant specialist (E. obesus) and a less acid-tolerant generalist (L. gibbosus).

Sodium and chloride transport in the large intestine of potassium-loaded rats

Increased dietary potassium ("potassium loading") induces several adaptive changes in colonic function, including increased potential-dependent potassium secretion, active potassium secretion, and Na-K-ATPase activity, but does not alter net sodium absorption in vivo. To establish whether potassium loading stimulates active sodium transport, unidirectional, net sodium, and chloride fluxes were determined under voltage-clamp conditions across isolated rat distal colonic mucosa. In normal animals net sodium flux (JNanet), net chloride flux (JClnet) and short-circuit current (Isc) were 6.1 +/- 1.1, 8.4 +/- 1.0, and 0.7 +/- 0.1 mu eq X h-1. cm-2, respectively; potassium loading significantly increased JNanet and Isc by 4.9 +/- 1.4 and 3.5 +/- 0.7 mu eq X h-1 X cm-2, respectively, without changing JClnet. Amiloride (0.1 mM) inhibited the increases in JNanet and Isc produced by potassium loading. In Cl-free Ringer solution in normal animals JNanet was reduced to 0.6 +/- 0.3 mu eq X h-1 X cm-2. Potassium loading produced identical increases in JNanet and Isc, which were also completely inhibited by 0.1 mM amiloride. These studies establish that potassium loading induces amiloride-sensitive electrogenic sodium absorption without affecting electroneutral sodium-chloride absorption.

Influence of Water Hardness, pH, and Alkalinity on the Mechanisms of Copper Toxicity in Juvenile Rainbow Trout,Salmo gairdneri

Juvenile rainbow trout were exposed to 25–400 μg copper∙L−1for 24 h. Water hardness, pH, and alkalinity were varied independently at a constant [Na+]. Net and unidirectional sodium fluxes were measured in hard and soft, low-alkalinity water and in hard, high-alkalinity water at neutral pH and pH 5.0. In low alkalinity water, Na+uptake (Jin) was inhibited at copper concentrations as low as 25 μg∙L−1, and sodium efflux (Jout) was stimulated above 100 μg∙L−1. High-alkalinity water significantly reduced the effects of copper on Jinand Jout, but there was no significant effect of increasing water hardness. The effects of pH 5.0 and copper were additive from 25 to 100 μg∙L−1, but a pure copper effect was found from 200 to 400 μg∙L−1. Fish died when they had lost about 50–55% of their exchangeable Na+pool. Water hardness and alkalinity had no effect on the apparent uptake of copper, but copper uptake was reduced by about 50% at pH 5.0.

Cutaneous Ion Transport in the Freshwater Teleost Synbranchus marmoratus

The gills of Synbranchus marmoratus become isolated from water for long periods of time while this fish breaths air or resides in moist burrows. In order to evaluate how interruptions in gill/water contact affect ionic regulation, we have undertaken urine collections and measurements of net and unidirectional sodium fluxes on intact, conscious fish. Comparative ionic flux measurements were made on the lungfishes Lepidosiren paradoxa and Protopterus spp. All three species demonstrated Na⁺ influx rates that are low for fish and freshwater vertebrates in general. Synbranchus marmoratus has an affinity ($K_{m}$) of 0.45 mM and a capacity ($J_{max}$) of 41.1 μEq/kg h⁻±, suggesting a relatively low-affinity, low-capacity ion transport system. The transepithelial potential difference measured between the bath and extracellular fluid was -7 mV (inside reference); thus the fluxes could not be accounted for by passive transport mechanisms (Ussing criterion). Synbranchus marmoratus has both a low urine flow (1.8 ml/...

Evidence that prostaglandin E2 stimulates chloride secretion in cultured A6 renal epithelial cells.

The effects of prostaglandin E2 (PGE2) on the transport of sodium and chloride were studied in cultured A6 renal epithelial cells. PGE2 on the basolateral but not the apical surface increased transmonolayer short-circuit current (Isc) and conductance. These changes could not be inhibited with amiloride or furosemide in the apical medium. Flux measurements showed that although Isc and net flux of sodium were equal in unstimulated cells, after addition of PGE2 the current increased with no corresponding changes in bidirectional or net flux of sodium. Immersing the cells in sodium-free or chloride-free media inhibited the effects of PGE2. Measurements of the simultaneous fluxes of sodium and chloride showed that after PGE2 was added there was a net flux of chloride from the basal to the apical side (secretion) that was equal to the change in Isc. The effects of PGE2 were inhibited by furosemide in the basal medium. We conclude that PGE2 stimulates a process of chloride secretion in A6 cells.

ECTOMYCORRHIZAS AFFECT IONIC BALANCE DURING AMMONIUM UPTAKE BY DOUGLAS‐FIR ROOTS

SUMMARYMycorrhizas have been shown to alter ion fluxes for many nutrients. Experiments were done to determine the extent to which ectomycorrhizas alter the ionic balance of roots of Douglas‐fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings mycorrhizal with Hebeloma crustuliniforme (Bull, ex St. Amans) Qúel. exposed to solutions containing either 16N ammonium sulphate or 16N ammonium chloride. Net fluxes of ammonium, hydrogen, potassium, calcium, sodium, bicarbonate, sulphate and chloride were measured. The mycorrhizal association altered ion fluxes, primarily decreasing sodium uptake and potassium release rates (both anion treatments) and increasing bicarbonate release during exposure to ammonium chloride. Rates of carboxylate accumulation in the tissue were inferred from the net flux data; mycorrhizal seedlings may produce more cation‐carboxylate complexes compared with nonmycorrhizal seedlings. When compared with agricultural plants exposed to ammonium, Douglas‐fir took up a considerably greater number of cations for each ammonium ion absorbed, which may account for the greater number of carboxylate anions also produced by Douglas‐fir. These findings were discussed in terms of ecological significance for growth of Douglas‐fir.

Inhibitin: a specific inhibitor of sodium/sodium exchange in erythrocytes.

An inhibitor of ouabain-insensitive sodium/sodium exchange in erythrocytes has been isolated from leukemic promyelocytes. To explore the specific effects of this inhibitor, named inhibitin, sodium transport experiments were carried out in human erythrocytes. Inhibitin reduced ouabain-insensitive bidirectional sodium transport. It did not change net sodium fluxes, had no significant effect on rubidium influx, and did not inhibit sodium-potassium-ATPase activity. The inhibitory effect of inhibitin was studied on sodium/sodium exchange and on sodium/lithium countertransport in 140 mM sodium and in sodium-free media. In the presence of sodium, inhibitin reduced sodium and lithium efflux to that observed in sodium-free medium. Inhibitin showed no reduction in sodium or lithium efflux when sodium was replaced by choline chloride or Mg2+. When inhibitin was combined with one or more of the other transport inhibitors (i.e., ouabain, furosemide, or bumetanide and amiloride), its inhibitable component remained distinct and it did not overlap with that of the other inhibitors. These studies show that inhibitin is a specific inhibitor of carrier-mediated sodium/sodium exchange and sodium/lithium countertransport processes in human erythrocytes.

BSS and BSS-plus: effect on corneal endothelial ionic and non-ionic fluxes

Rabbit corneas were mounted in water jacketed chambers and the endothelial surface perfused with either BSS (Balanced Salt Solution) or BSS-Plus for 3 hr. Unidirectional and net fluxes of sodium were similar in both groups of corneas. Bicarbonate fluxes in BSS-Plus were statistically similar to those in Krebs-Ringer solution. Bicarbonate fluxes could not be determined with BSS because the solution does not contain bicarbonate. In addition, there was no statistically significant alteration of inulin or dextran permeability when comparing perfusion with BSS and BSS-Plus. From this study it appears that BSS and BSS-Plus are comparable in their ability to maintain corneal endothelial physiologic function during in-vitro perfusion. This is in contrast to previous work which showed that BSS-Plus induced less endothelial morphologic change than BSS. It is concluded that morphologic alterations may be more sensitive parameters of endothelial stress than are fluxes and permeabilities.

Lymphocyte abnormalities in three types of hypertension in the rat.

Lymphocyte number and weight and their sodium and potassium contents and net passive fluxes were measured in spontaneously hypertensive stroke-prone rats, deoxycorticosterone acetate-treated rats, and two-kidney, one clip renal hypertensive rats. Wistar-Kyoto rats were used as controls for the spontaneously hypertensive stroke-prone rats, and normal intact Sprague-Dawley rats were used as controls for the others. Blood lymphocyte count was higher and lymphocyte weight was lower in the hypertensive rats. Intralymphocytic sodium content (millimoles per kilogram of dry weight) was elevated in the three forms of hypertension as compared with control values (spontaneously hypertensive stroke-prone rats, 43.0 +/- 1.7 vs Wistar-Kyoto rats, 37.3 +/- 1.3; deoxycorticosterone acetate-treated rats, 44.4 +/- 3.1 vs Sprague-Dawley rats, 36.1 +/- 1.7; one-kidney, one clip rats, 50.5 +/- 3.7 vs Sprague-Dawley rats, 38.9 +/- 2.0). Intralymphocytic potassium content was not significantly altered in any of the forms of hypertension. Lymphocytes from spontaneously hypertensive stroke-prone rats and deoxycorticosterone acetate-treated rats exhibited elevated net sodium fluxes (millimoles per kilogram of dry weight per hour) as compared with those of controls (spontaneously hypertensive stroke-prone rats, 7.00 +/- 0.99 vs Wistar-Kyoto rats, 4.89 +/- 0.63; deoxycorticosterone acetate-treated rats, 7.58 +/- 0.97 vs Sprague-Dawley rats, 5.6 +/- 0.64). Net potassium fluxes were significantly elevated only in the spontaneously hypertensive stroke-prone rats (14.07 +/- 1.70 vs 8.23 +/- 1.04 in Wistar-Kyoto rats). Sodium and potassium fluxes in lymphocytes from two-kidney, one clip rats and Sprague-Dawley rats were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine stimulates sodium transport in kidney A6 epithelia in culture.

The effects of adenosine receptor agonists and antagonists were examined in epithelia formed in culture by A6 cells, a continuous cell line derived from Xenopus laevis kidney. A6 epithelia have a high electrical resistance and a short-circuit current that is equal to net sodium flux from mucosal to serosal surface. Adenosine, 2-chloroadenosine, 5'-(N-ethyl)carboxamidoadenosine, and N6-(L-2-phenylisopropyl) adenosine produced concentration-dependent increases in short-circuit current. Stimulation of short-circuit current by 2-chloroadenosine occurred at concentrations of 0.05 microM and above, with half-maximal stimulation occurring at 0.3 microM. 5'-(N-ethyl)carboxamidoadenosine was more potent than N6-(L-2-phenylisopropyl)adenosine, the usual order of potency for activation of stimulatory adenosine receptors. Theophylline (100 microM), an adenosine receptor antagonist, reduced the short-circuit current response to adenosine and 2-chloroadenosine by 85-90%. Amiloride, an agent that inhibits both basal and adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated short-circuit current in A6 epithelia, completely and reversibly inhibited short-circuit current stimulated by 2-chloroadenosine. Adenosine and 2-chloroadenosine stimulated adenylate cyclase activity in a crude membrane preparation from A6 cells. Stimulation by adenosine was blocked by adenosine deaminase. 2-Chloroadenosine increased cell cAMP accumulation in intact epithelia. The results provide evidence that adenosine and adenosine receptor agonists stimulate adenylate cyclase and active sodium transport in an epithelial cell line of renal origin.

Water and electrolyte transport in Henle's loop and distal tubule after renal sympathectomy in the rat.

The effect of acute renal denervation (AD) on transtubular movement of water and electrolytes in Henle's loop (LH) and distal tubule (DT) of superficial nephrons was studied by the technique of in vivo microperfusion in Inactin-anesthetized hydropenic male rats. In time-control experiments (n = 6) no changes in either whole kidney or single nephron function were detected. Predenervation results of denervation experiments (n = 10) were similar to those of the time-control series. AD resulted in increased urine, sodium, and potassium excretion in the absence of changes of either arterial blood pressure or GFR. Compared with predenervation data, AD led to significant decreases in net transtubular fluxes (J) of water and sodium in both perfused segments with delivery kept constant (delta JNa: LH = 144 +/- 26 peq X min-1, 9.1 +/- 0.3%; DT = 94 +/- 11 peq X min-1, 22.3 +/- 1.1%). Potassium absorption in the loop decreased but an increase in net addition (secretion) of K in the distal tubule on denervation occurred (delta JK = 8.7 +/- 1.9 peq X min-1, 68.7 +/- 3.2%). Use of the reperfusion technique gave similar results. These results indicate that efferent renal sympathetic nerve activity directly influences water, sodium, and potassium transport in the loop of Henle and distal tubule of the anesthetized rat.

Effects of sulfodeoxycholate on rat and rabbit small intestine.

To determine how sulfation alters the biological properties of dihydroxy bile acids, we compared the effects of 3-sulfodeoxycholate (SDC) and deoxycholate (DC) in the rat and rabbit intestine. While 5 mM DC induced water and electrolyte secretion and inhibited glucose absorption in the rat, SDC enhanced jejunal and ileal water and solute absorption. SDC had no effect in the rabbit ileum. In the rat jejunum DC caused mucosal injury and enhanced mucosal permeability while SDC had no effect. In vitro in the rabbit ileum, 10 mM SDC enhanced net sodium flux and decreased net residual flux, while 0.5 mM DC reduced net sodium flux and induced Cl- secretion. Both bile acids increased short-circuit current and potential difference and decreased tissue conductance. During reversed-phase, high-performance liquid chromatography SDC was more polar than DC. Sulfation reduced the ability of DC to destroy large unilamellar liposomes by a factor of 10. Thus, sulfation abolishes the effects of DC on the intestine by enhancing the polarity of this molecule. The enhancement of intestinal solute and water absorption by SDC requires further study.