Effect of osmolality on renal medullary Na-K-ATPase activity in the postobstructive kidney

Knox, William H.; Sax, Julian; Wilson, Donald R.; Sen, Amar K.

doi:10.1139/y77-153

Cited by 7 publications

(6 citation statements)

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“…Thus, isolated perfused mTAL from obstructed kidneys reabsorb Cl-less effectively than tubules from control kidneys (8). In addition, measurements of medullary tonicity have demonstrated medullary washout in obstructed kidneys, suggesting a defect in mTAL transport of solutes into the interstitium (24,26). Although deficient mTAL sodium transport contributes to salt wasting in obstruction, the specific mechanisms underlying this defect remain unclear.…”

Section: Resultsmentioning

confidence: 99%

Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy.

Hwang¹,

Haas²,

Harris³

et al. 1993

J. Clin. Invest.

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To characterize the sodium transport defect responsible for salt wasting in obstructive nephropathy, the major sodium transporters in the medullary thick ascending limb (mTAL), the apical Na-K-2CI cotransporter and the basolateral Na-KATPase, were studied in fresh suspensions of mTAL cells and outer medulla plasma membranes prepared from obstructed and untreated kidneys. Oxygen consumption (Qo2) studies in intact cells revealed marked reductions in the inhibitory effects of both furosemide and ouabain on Qo2 in cells from obstructed, as compared with control animals, indicating a reduction in activities of both the Na-K-2CI cotransporter and the Na-K-ATPase. Saturable [3Hlbumetanide binding was reduced in membranes isolated from obstructed kidneys, but the Kd for 13H Ibumetanide was unchanged, indicating a decrease in the number of functional luminal Na-K-2CI cotransporters in obstructed mTAL. Ouabain sensitive Na-K-ATPase activity in plasma membranes was also reduced, and immunoblots using specific monoclonal antibodies directed against the a and ,B subunits of rabbit Na-K-ATPase showed decreased amounts of both subunits in outer medullas of obstructed kidney. A significant decrease in I3HIbumetanide binding was detected after 4 h of ureteral obstruction, whereas Na-K-ATPase activity at this time was still not different from control. We conclude that ureteral obstruction reduces the amounts of both luminal Na-K-2CI cotransporter and basolateral Na-K-ATPase in mTAL of obstructed kidney and that these reductions contribute to the salt wasting observed after release of obstruction. (J. Clin. Invest. 1993. 91:21-28).

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Section: Resultsmentioning

confidence: 99%

Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy.

Hwang¹,

Haas²,

Harris³

et al. 1993

J. Clin. Invest.

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“…Increased activation of Na-K-activated adenosine triphosphatase occurs under these conditions , though whether this increase is brought about by osmotic stress per se or whether it is results from increased concentrations of ions such as Na and Cl may depend not only upon the species but also upon the experimental conditions (see for example the recent studies on activity of this enzyme in rat kidney by Knox, Sax, Wilson & Sen (1977)). …”

Section: Introductionmentioning

confidence: 99%

The influence of chloride ions on renal outer medullary cell volume.

Law¹

1979

The Journal of Physiology

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SUMMARY1. Slices of rat renal outer medulla have been incubated in media made hyperosmotic (540 and 1055 m-osmole/kg H20) by the addition of urea, and containing variable concentrations of Cl (90, 144, 189 and 215 mM) and constant concentrations of Na (180 mM) and K (5.9 mM). A small number of incubations have been conducted in the presence of 100 mM-Na.2. Changes in cell volume during incubation have been calculated on the basis of initial and final slice weight and inulin space.3. The capacity of cells to shrink in response to extracellular osmotic stress was related principally to the external Cl concentration rather than to osmolality, increases in concentration being associated with enhanced shrinkage. Shrinkage was accompanied by net loss of cellular Cl. The ratio between intra-and extracellular C1 concentration (ca. 0.41) remained constant in all media.4. In media containing low Cl concentration (90 mM), reduction of media Na concentration to 100 mM enhanced shrinkage. This effect was not observed when medium Cl concentration was greater than 90 mM.5. Ethacrynic acid-cysteine (1 mM) significantly impaired the shrinkage response to extracellular osmotic stress, and caused cell swelling in media of relatively low Cl concentration and osmolality. It did not abolish the dependency of cell volume upon Cl concentration. There was marked reduction in the net amount of Cl lost from cells. 6. Ethacrynic acid-cysteine caused an increase in cellular Na content only in media containing 540 m-osmole/kg H20 and Cl concentrations less than 215 mm.7. Ouabain (1 mM) inhibited cell shrinkage to a lesser extent than ethacrynic acidcysteine in all media except that causing the greatest shrinkage under control conditions (215 mM-Cl/1055 m-osmole/kg H20). It is suggested that a ouabain-sensitive process may play an increasingly important role in Cl-related cell shrinkage as this becomes more pronounced.8. The findings are consistent with the view that Cl ions influence cell volume both through their effective external osmotic pressure and by means of Cl-specific process; the latter is associated with net loss of cellular Cl. A dependence of this loss upon Na/K exchange-linked metabolism is inferred, but the present findings do not permit the active or passive nature of the extrusion to be defined.

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“…However, the two series of experiments are not strictly comparable, since osmolality was increased by cycloleueine in the earlier experiments. As far as a possible increase in ATPase activity is concerned, although Knox et al (1977) found an increase in renal medullary ATPase activity when osmolality was increased with NaCI, there was no increase when sucrose was used. This suggests that the stimulation might have been via an increased substrate (sodium) concentration.…”

Section: Discussionmentioning

confidence: 91%

“…In this tissue, hyperosmolar solutions applied on both sides at once reduced the short-circuit current, oxygen consumption and active sodium transport (Bentley et al, 1973). In contrast, the activity of the renal medullary Na/K ATPase has been shown to increase with increasing osmolality of the medium bathing the slice (Knox et al, 1977). Accordingly, it was decided to investigate what effect, if any.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Changes in Osmolality on Amino Acid Transport in the Proximal Convoluted Tubule of the Rat Kidney

1981

Aust J Exp Biol Med

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Summary. In order to differentiate between the efTect of increased amino acid (substrate) concentration and the accompanying rise in fluid osmolality on renai tubular amino acid transport properties. Ihe transport of cycloleucine has been examined under conditions where ihe osmolality only was altered with raffinose. In stationary micro perfusion experiments it has been demonstrated that an increase in osmolality to 400 mosmol/kg on both sides of the epithelium at once does not alter the active transporting capacity achieved. Although no experimental evidence is yet available, theoretical considerations suggest that neither component of this active transporting capacity, viz. active transepithelial transport rate or the permeability coefTicient, would have changed, INTRODUCTIONEarlier stationary microperfusion studies of amino acid transport in the proximal convoluted tubule of the rat kidney had shown that the capacity for reabsorption decreased at sites further removed from the glomerulus (Lingard, Rumrich and Young, 1973a). In an attempt to define the cause of this decreased transporting capacity, the kinetics of the transport system were studied by changing the amino acid concentration of both the luminal and peritubular capillary perfusates over a wide range (Lingard, Rumrich and Young, 1973b; Lingard, Gyory and Young, 1975). In these experiments, atnino acid was added to both the luminal and peritubular capillary perfusates whose composition otherwise remained fixed, in order to keep the concentrations of the electrolyte components constant. This meant that the total osmolality of both the luminal and peritubuiar capillary perfusates increased with increasing amino acid concentration. The question thus arose as to whether the amino acid transport rates at the higher concentrations (and thus also the kinetic analysis) could have been affected by the fact that the perfusates were hypertonic.Evidence is available that changes in the osmotic pressure of the bathing fluid can affect transport properties of an epithelium, and, not surprisingly, the

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Effect of osmolality on renal medullary Na-K-ATPase activity in the postobstructive kidney

Cited by 7 publications

References 0 publications

Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy.

Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy.

The influence of chloride ions on renal outer medullary cell volume.

The Effect of Changes in Osmolality on Amino Acid Transport in the Proximal Convoluted Tubule of the Rat Kidney

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