Reflection coefficients and water permeability in rat proximal tubule

1989 ◽  
Vol 257 (4) ◽  
pp. F658-F668 ◽  
Author(s):  
R. Green ◽  
G. Giebisch
Keyword(s):  
Proximal Tubule ◽  
Water Permeability ◽  
Significant Contribution ◽  
Water Flux ◽  
Reflection Coefficients ◽  
Ionic Fluxes ◽  
Peritubular Capillaries ◽  
Solute Movement ◽  
Rat Proximal Tubule ◽  
Net Water Flux

Simultaneous microperfusion of proximal tubules and peritubular capillaries in kidneys of rats anesthetized with Inactin was used to measure reflection coefficients. All perfusates contained cyanide to inhibit active transport; the tubular perfusate was isotonic and the peritubular capillaries were perfused with solutions made hypertonic with NaCl, NaHCO3, L-glucose, or sodium ferrocyanide. Measurements of recollected fluid enabled a precise mean gradient and ionic fluxes to be calculated; net water flux was measured with inulin. Imposed gradients always partly dissipated. Reflection coefficients were 0.59 +/- 0.01 for NaCl, 0.87 +/- 0.04 for NaHCO3-, and 0.96 +/- 0.07 for ferrocyanide, assuming that L-glucose was 1. Water permeability of the proximal tubule was 1,030 microns/s. Ionic permeability of Cl- (21.6 +/- 1.3 X 10(-5) cm/s) was greater than that for Na+ (13.3 +/- 2.7 X 10(-5) cm/s); permeability for L-glucose was 5.4 +/- 1.3 X 10(-5), and for ferrocyanide ions 2.7 +/- 0.9 X 10(-5) cm/s. It is concluded that in rat proximal tubule both NaCl and NaHCO3 have reflection coefficients less than 1.0 and solute asymmetry across the epithelium is a significant driving force for fluid reabsorption. Furthermore the data suggest that there is a significant contribution of solvent drag to solute movement.

Glomerulotubular balance in a mathematical model of the proximal nephron

1990 ◽  
Vol 258 (3) ◽  
pp. F612-F626 ◽  
Author(s):  
A. M. Weinstein
Keyword(s):  
Tight Junction ◽  
Proximal Tubule ◽  
Water Permeability ◽  
Water Flux ◽  
Salt Transport ◽  
Salt Flux ◽  
Filtration Fraction ◽  
Epithelial Junctions ◽  
Permeability Increase ◽  
Glomerulotubular Balance

A nonelectrolyte model of proximal tubule epithelium has been extended by the inclusion of a compliant tight junction. Here "compliance" signifies that both the junctional salt and water permeability increase and the salt reflection coefficient decreases in response to small pressure differences from lateral interspace to tubule lumen. In previous models of rat proximal tubule, there has been virtually no sensitivity of isotonic salt transport to changes in peritubular oncotic force. With the inclusion of junctional compliance, decreases in peritubular protein can open the junction and produce a secretory salt flux. Thus the model can represent the "backflux hypothesis," as it was originally put forth (J. E. Lewy and E. E. Windhager, Am. J. Physiol. 214: 943-954, 1968). Additional calculations, simulating a tight junction with negligible water permeability, reveal that the quantitative impact of peritubular protein can be realized whether or not there is substantial junctional water flux. The epithelial model of proximal tubule has also been incorporated into a model of the proximal nephron, complete with glomerulus, peritubular capillary, and interstitium. The interstitial compartment is well mixed and interstitial pressure and osmolality are determined iteratively to achieve balance between tubule reabsorption and capillary uptake. For this model, two domains of operation are identified. When interstitial pressures are low, junctions are closed, and filtration fraction has no effect on proximal reabsorption. When interstitial pressures are relatively elevated, epithelial junctions are open, and proximal salt reabsorption changes in proportion to changes in filtration fraction. In neither domain, however, does the model tubule augment salt flux with isolated increases in luminal flow rate (at constant filtration fraction). The absence of a separate effect of tubule fluid flow on salt transport precludes perfect glomerulotubular balance.

Mechanisms of stimulation of proximal tubule chloride transport by formate and oxalate

1996 ◽  
Vol 271 (2) ◽  
pp. F446-F450 ◽  
Author(s):  
T. Wang ◽  
A. L. Egbert ◽  
T. Abbiati ◽  
P. S. Aronson ◽  
G. Giebisch
Keyword(s):  
Proximal Tubule ◽  
Chloride Transport ◽  
Rat Kidney ◽  
Exchange Process ◽  
Exchange Inhibitor ◽  
Volume Absorption ◽  
Peritubular Capillaries ◽  
Rat Proximal Tubule ◽  
Stimulation Of

We have previously demonstrated that formate and oxalate stimulate volume absorption in the rat proximal tubule, consistent with Cl-/formate and Cl-/oxalate exchange process across the apical membrane. To sustain Cl- absorption by these processes requires mechanisms for recycling formate and oxalate from lumen to cell. The aims of the present study were to characterize these mechanisms of formate and oxalate recycling. Proximal tubules and peritubular capillaries were simultaneously microperfused in the rat kidney in situ. Serum formate concentration was determined to be 56.5 +/- 7.7 microM. Addition of 5, 50, and 500 microM formate to both luminal and capillary perfusates significantly increased net Cl- absorption (Jcl) by 26, 26, and 46%, respectively. Jcl was stimulated 38% by 1 microM oxalate added to the perfusates. Removal of sulfate completely prevented the stimulation of Jcl by 1 microM oxalate but had no effect on the stimulation of Jcl by formate. Luminal addition of the Na+/H+ exchange inhibitor ethylisopropylamiloride completely blocked the stimulation of Jcl by 50 microM formate but had no effect on stimulation by oxalate. We conclude that physiological concentrations of formate and oxalate markedly stimulate Cl- and fluid absorption in the rat proximal convoluted tubule. Whereas formate recycling most likely involves Na+/H+ exchange in parallel with H(+)-coupled formate entry, oxalate recycling involves sodium-sulfate cotransport in parallel with sulfate/oxalate exchange.

Effects of formate and oxalate on volume absorption in rat proximal tubule

1992 ◽  
Vol 263 (1) ◽  
pp. F37-F42 ◽  
Author(s):  
T. Wang ◽  
G. Giebisch ◽  
P. S. Aronson
Keyword(s):  
Proximal Tubule ◽  
Channel Blocker ◽  
Ringer Solution ◽  
Proximal Tubules ◽  
Solution Ph ◽  
Physiological Range ◽  
Volume Absorption ◽  
Peritubular Capillaries ◽  
Rat Proximal Tubule

We examined the effects of formate and oxalate on the rate of fluid absorption (Jv) in the rat proximal convoluted tubule in situ. Proximal tubules were microperfused with a high-Cl-, low-HCO3- Ringer solution (pH 6.7), and the peritubular capillaries were perfused with a standard Ringer solution (pH 7.4), simulating conditions in the late proximal tubule. Jv, a measure of transtubular NaCl absorption under these conditions, was calculated from the change in luminal [3H]inulin. Addition of formate in the physiological range (500 microM) to the luminal perfusate increased Jv by 45%; addition of 500 microM formate to both luminal and capillary perfusates increased Jv by 57%. Similarly, addition of oxalate in the physiological range (5 microM) to the luminal perfusate increased Jv by 37%; addition of 5 microM oxalate to both luminal and capillary perfusates increased Jv by 57%. The stimulatory effects of formate and oxalate perfused in the lumen and capillaries were not additive. Addition of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS, 0.1 mM) to the luminal perfusate had no effect on baseline Jv measured in the absence of added formate and oxalate but completely abolished the increment in Jv induced by formate and oxalate. Addition of the Cl(-)-channel blocker diphenylamine-2-carboxylate (DPC, 0.2 mM) to the capillary perfusate had no effect on baseline Jv but completely abolished the increment in Jv induced by formate and oxalate.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct evaluation of the permeability of the rat proximal convoluted tubule to CO2

1982 ◽  
Vol 242 (5) ◽  
pp. F470-F476
Author(s):  
M. S. Lucci ◽  
L. R. Pucacco ◽  
N. W. Carter ◽  
T. D. DuBose
Keyword(s):  
Carbonic Anhydrase ◽  
Proximal Tubule ◽  
Carbonic Acid ◽  
Carbonic Anhydrase Activity ◽  
Proximal Convoluted Tubule ◽  
Direct Evaluation ◽  
Carbon Dioxide Gas ◽  
Peritubular Capillaries ◽  
Rat Proximal Tubule

Conflicting data exist regarding the ability of the rat proximal convoluted tubule to maintain a transepithelial gradient for CO2 and the effects of carbonic anhydrase on CO2 permeability. The present in vivo microperfusion experiments were designed to assess the ability of the rat proximal tubule to sustain a CO2 gradient between tubule lumen and peritubular blood. Tubules were perfused at rates ranging from 10 to 100 nl/min with isotonic sodium chloride containing no CO2. Peritubular capillary and intraluminal PCO2 was measured during microperfusion with PCO2 microelectrodes to allow determination of the transepithelial CO2 gradient. The mean PCO2 measured in peritubular capillaries of control rats was 60.6 +/- 1.9 mmHg. Since the perfusion solution initially contained no CO2, a gradient of 60 mmHg was imposed across the tubule epithelium. Intraluminal PCO2 rapidly approached that of the surrounding capillaries. At a tubule perfusion rate of 20 nl/min, the gradient between lumen and blood decreased to 0.9 mmHg, a value not significantly greater than zero. The calculated CO2 permeability coefficient (KCO2) was 3.69 X 10(-5) cm2/s. Addition of either 10(-4) M acetazolamide or benzolamide did not prolong the rapid dissipation of the imposed CO2 gradient. The KCO2 during carbonic anhydrase inhibition was not significantly different from control values. It is concluded that the rat proximal tubule does not present a physiologically significant diffusion barrier to CO2 either in the presence or absence of carbonic anhydrase activity. The previously demonstrated acid disequilibrium pH in the proximal tubule during inhibition of carbonic anhydrase represents an intraluminal accumulation of carbonic acid rather than of carbon dioxide gas.

A dual-pathway ultrastructural model for the tight junction of rat proximal tubule epithelium

2003 ◽  
Vol 285 (2) ◽  
pp. F241-F257 ◽  
Author(s):  
Peng Guo ◽  
Alan M. Weinstein ◽  
Sheldon Weinbaum
Keyword(s):  
Tight Junction ◽  
Proximal Tubule ◽  
Water Permeability ◽  
Pore Radius ◽  
Pathway Model ◽  
Small Pore ◽  
Order Of Magnitude ◽  
Dual Pathway ◽  
Ultrastructural Model ◽  
Rat Proximal Tubule

A dual-pathway model is proposed for transport across the tight junction (TJ) in rat proximal tubule: large slit breaks formed by infrequent discontinuities in the TJ complex and numerous small circular pores, with spacing similar to that of claudin-2. This dual-pathway model is developed in the context of a proximal tubule model (Weinstein AM. Am J Physiol Renal Fluid Electrolyte Physiol 247: F848–F862, 1984) to provide an ultrastructural view of solute and water fluxes. Tubule model paramters (TJ reflection coefficient and water permeability), plus the measured epithelial NaCl and sucrose permeabilities, provide constraints for the dual-pathway model, which yields the small-pore radius and spacing and large slit height and area. For a small-pore spacing of 20.2 nm, comparable to the distance between adjacent particle pairs in apposing TJ strands, the small-pore radius is 0.668 nm and the large slit breaks have a height of 19.6 nm, occupying 0.04% of the total TJ length. This pore/slit geometry also satisfies the measured permeability for mannitol. The numerous small circular pores account for 91.25% of TJ NaCl permeability but only 5.0% of TJ water permeability. The infrequent large slit breaks in the TJ account for 95.0% of TJ water permeability but only 8.7% of TJ NaCl permeability. Sucrose and mannitol (4.6- and 3.6-Å radius) can pass through both the large slit breaks and the small pores. For sucrose, 78.3% of the flux is via the slits and 21.7% via the pores; for mannitol, the flux is split nearly evenly between the two pathways, 50.8 and 49.2%. In this ultrastructural model, the TJ water permeability is 21.2% of the entire transepithelial water permeability and thus an order of magnitude greater than that predicted by the single-pore/slit theory (Preisig PA and Berry CA. Am J Physiol Renal Fluid Electrolyte Physiol 249: F124–F131, 1985).

scholarly journals Convective paracellular solute flux. A source of ion-ion interaction in the epithelial transport equations.

1987 ◽  
Vol 89 (3) ◽  
pp. 501-518 ◽  
Author(s):  
A M Weinstein
Keyword(s):  
Proximal Tubule ◽  
Epithelial Transport ◽  
Electrical Potential ◽  
Transport Equations ◽  
Solute Flux ◽  
Reflection Coefficients ◽  
Cross Term ◽  
Parallel Structures ◽  
In Series ◽  
Rat Proximal Tubule

An electrolyte model of an epithelium (a cell and a tight junction in parallel, both in series with a lateral interspace basement membrane) is analyzed using the formalism of nonequilibrium thermodynamics. It is shown that if the parallel structures are heteroporous (i.e., reflection coefficients for two ion species differ between the components), then a cross-term will appear in the overall transport equations of the epithelium. Formally, this cross-term represents an ion-ion interaction. With respect to the rat proximal tubule, data indicating epithelial ionic reflection coefficients less than unity, together with the assumption of no transcellular solvent drag, imply the presence of convective paracellular solute flux. This means that a model applicable to a heteroporous structure must be used to represent the tubule, and, in particular, the cross-terms for ion-ion interaction must also be evaluated in permeability determinations. A series of calculations is presented that permits the estimation of the Na-Cl interaction for rat proximal tubule from available experimental data. One consequence of tubule heteroporosity is that an electrical potential may be substantially less effective than an equivalent concentration gradient in driving reabsorptive ion fluxes.

Osmotic forces driving water reabsorption in the proximal tubule of the rat kidney

1989 ◽  
Vol 257 (4) ◽  
pp. F669-F675 ◽  
Author(s):  
R. Green ◽  
G. Giebisch
Keyword(s):  
Reflection Coefficient ◽  
Water Permeability ◽  
Rat Kidney ◽  
Proximal Tubules ◽  
Osmotic Gradient ◽  
Water Reabsorption ◽  
Fluid Flux ◽  
Fluid Reabsorption ◽  
Ionic Fluxes ◽  
Peritubular Capillaries

Simultaneous microperfusion of proximal tubules and peritubular capillaries in kidneys of rats anesthetized with Inactin was used to measure reabsorption of fluid in response to an imposed osmotic gradient. The tubular fluid was isotonic and the peritubular capillaries were made hypertonic with NaCl or NaHCO3. Mean gradients and ionic fluxes were measured. When no gradient was imposed tubular fluid became hypotonic and rate of fluid reabsorption was 0.700 nl.mm-1.min-1. Imposition of a 25 mM NaCl gradient increased fluid flux to 3.887 nl.mm-1.min-1, whereas 25 mM NaHCO3 stimulated 5.226 ml/mm fluid reabsorption. This gave a relative reflection coefficient of NaCl:NaHCO3 of 0.73. Apparent water permeability varied with highest values for the smallest gradients. This suggests the possibility of a compartment in the epithelium that is hypertonic to the peritubular capillaries. The hypertonicity required to account for fluid movement was 6-16 mosmol/kg.

Single proximal tubules of the Necturus kidney. III. Dependence of H2O movement on NaCl concentration

1959 ◽  
Vol 197 (2) ◽  
pp. 313-318 ◽  
Author(s):  
Erich E. Windhager ◽  
Guillermo Whittembury ◽  
Donald E. Oken ◽  
Hans J. Schatzmann ◽  
A. K. Solomon
Keyword(s):  
Water Movement ◽  
Water Flux ◽  
Potential Gradient ◽  
Solute Flux ◽  
Experimental Conditions ◽  
Nacl Concentration ◽  
Proximal Tubular ◽  
Solute Movement ◽  
The Relationship ◽  
Net Water Flux

Stopped flow microperfusion technique ( Am. J. Physiol. 195: 563, 1958) was used to study water movement across the proximal tubular wall of Necturus kidney. In 23 experiments, net water movement was measured from perfusion solutions containing 50, 62.5, 75 and 100 mEq. NaCl/1. which were made isosmotic with Necturus plasma by addition of mannitol. Water movement was shown to depend upon luminal NaCl concentration. Studies of the relationship between net solute flux and water flux demonstrated a linear relationship: net water flux (mµl/sec.) = 9.4 x net solute flux + 0.003. Net water flux is statistically zero when net solute flux is zero. Under these experimental conditions no force is important for water movement other than that arising from solute movement. It is concluded that net movement of Na has taken place up an electrochemical potential gradient, indicating active transport of this ion. Furthermore, movement of water from the tubule is considered to be passive since net water flux may be accounted for quantitatively in terms of osmotically induced forces arising from net solute movement.

Effects of lysine on bicarbonate and fluid absorption in the rat proximal tubule

1982 ◽  
Vol 242 (6) ◽  
pp. F604-F609
Author(s):  
Y. L. Chan ◽  
N. A. Kurtzman
Keyword(s):  
Proximal Tubule ◽  
Inhibitory Effect ◽  
Ringer Solution ◽  
Glass Electrode ◽  
Capillary Perfusion ◽  
Fluid Reabsorption ◽  
Bicarbonate Reabsorption ◽  
Peritubular Capillaries ◽  
Lysine Concentration ◽  
Rat Proximal Tubule

The effects of lysine on bicarbonate and fluid reabsorption in the rat proximal tubule were studied by luminal and capillary perfusion in situ. The proximal tubule and peritubular capillaries were perfused with bicarbonate Ringer solution containing [14C]inulin. The rate of bicarbonate reabsorption (JHCO3) was estimated to be 124 +/- 9.5 peq.min-1.mm-1 using a pH membrane glass electrode. The rate of net fluid reabsorption (Jv) was 2.6 +/- 0.21 nl.min-1.mm-1. When 10 mM L-lysine was added to the luminal perfusate, a 35% reduction in JHCO3 and no change in Jv were observed. Increase of L-lysine concentration in the luminal perfusate to 20 mM did not reduce JHCO3 further nor did it influence Jv.l When 10 mM L-lysine was added to the capillary perfusate, a 13% reduction in JHCO3 was observed (NS). Increase of lysine concentration in the capillary perfusate to 20 mM significantly reduced JHCO3 by 26% (P less than 0.01). There was no significant change in Jv under both conditions. The effect of L-lysine in the lumen was related to its reabsorption kinetics, D-Lysine, which was not reabsorbed significantly, did not affect bicarbonate reabsorption in the proximal tubule. These results indicate that the inhibitory effect of L-lysine is related to the entry of lysine into the cell from the lumen.

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