Proton secretion by the kidney.
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Animals↗
Biomedical subjects
F C Rector
Publications and source records attributed to F C Rector.
Carbonic anhydrase-dependent bicarbonate reabsorption in the rat proximal tubule.
The extent to which bicarbonate reabsorption in the rat proximal convoluted tubule depends on carbonic anhydrase has been examined by in vivo microperfusion and the measurement of total CO2 concentration by microcalorimetry. Tubules were perfused with an ultrafiltrate-like solution at 13 nl/min, and volume reabsorptive rate (JV) was measured using [14C]inulin. Addition of either 800 or 100 microM acetazolamide to the perfusion solution completely inhibited the reabsorption of total CO2. The control total CO2 reabsorptive rate (JtCO2) was 147 +/- 23 pmol/mm.min, and acetazolamide reduced JtCO2 to -3 +/- 5 pmol/mm.min. Acetazolamide reduced JV by 65% from a control of 2.3 +/- 0.4 to 0.8 +/- 0.1 nl/mm.min. The dose-response curve for acetazolamide showed that the I50 for inhibition of JtCO2 was 4 microM. The inactive congener of acetazolamide, t-butyl acetazolamide, did not reduce JV or inhibit bicarbonate reabsorption, indicating that the effect of acetazolamide on JtCO2 was specific for carbonic anhydrase inhibition. Since bicarbonate reabsorption was completely blocked by carbonic anhydrase inhibition, there is no need to postulate either carbonic acid recycling or carbonic anhydrase-independent bicarbonate reabsorption.
Acetazolamide↗
Effect of acetazolamide on bicarbonate reabsorption in the proximal tubule of the rat.
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Acetazolamide↗
Control of proximal bicarbonate reabsorption in normal and acidotic rats.
This free-flow micropuncture study examined the dependence of bicarbonate reabsorption in the rat superficial proximal convoluted tubule to changes in filtered bicarbonate load, and thereby the contribution of the proximal tubule to the whole kidney's response to such changes. The independent effects of extracellular fluid (ECF) volume expansion and of acidosis on proximal bicarbonate reabsorption were also examined. When the plasma volume contraction incurred by the micropuncture preparatory surgery was corrected by isoncotic plasma infusion ( congruent with1.3% body wt), single nephron glomerular filtration rate (SNGFR), and the filtered total CO(2) load increased by 50%. Absolute proximal reabsorption of total CO(2) (measured by microcalorimetry) increased by 30%, from 808+/-47 during volume contraction to 1,081+/-57 pmol/min.g kidney wt after plasma repletion, as fractional total CO(2) reabsorption decreased from 0.90 to 0.77. Aortic constriction in these plasma-repleted rats returned the filtered load and reabsorption of total CO(2) to the previous volume contracted levels. In other animals isohydric ECF expansion with plasma (5% body wt) or Ringer's solution (10% body wt), or both, produced no further diminution in fractional proximal total CO(2) reabsorption (0.76-0.81). Metabolic acidosis was associated with very high fractional proximal total CO(2) reabsorptive rates of 0.82 to 0.91 over a wide range of SNGFR and ECF volumes. At a single level of SNGFR, end-proximal total CO(2) concentration progressively decreased from 5.6+/-0.5 to 1.6 +/-0.2 mM as arterial pH fell from 7.4 to 7.1. Expansion of ECF volume in the acidotic rats did not inhibit the ability of the proximal tubule to lower end-proximal total CO(2) concentrations to minimal levels. In conclusion, bicarbonate reabsorption in the superficial proximal convoluted tubule is highly load-dependent (75-90%) in normal and acidotic rats. No inhibitory effect of ECF volume per se on proximal bicarbonate reabsorption, independent of altering the filtered bicarbonate load, could be discerned. Acidosis enabled the end-proximal luminal bicarbonate concentration to fall below normal values and reduced distal bicarbonate delivery.
Absorption↗
Ion selectivity and proximal salt reabsorption.
Electrophysiological techniques were used in isolated perfused superficial (S) and juxtamedullary (JM) rabbit proximal convoluted tubules (PCT) to examine the relative sodium-to-chloride (PNa/PCl) and bicarbonate-to-chloride (PHCO3/PCl) permeability ratios. We found that the great majority of PCT are sodium selective and that PHCO3/PCl depends on the experimental conditions. In the presence of active sodium transport, PHCO3/PCl is high and increases with PNa/PCl. When PHCO3/PCl is determined after inhibition of active sodium transport or at 25 degrees C, PHCO3/PCl approximates the free solution anion mobility ratio of 0.5 and is independent of PNa/PCl. The difference between PHCO3/PCl determined in the presence of and in the absence of active transport suggests that the lowering of bath bicarbonate concentration in the presence of active transport changes both paracellular and transcellular current flow. In addition, we found that during luminal perfusion with high chloride, low bicarbonate, organic solute-free solutions, the transepithelial electrical potential depends on PNa/PCl and PHCO3/PCl. This potential is approximately 4.0 mV in S PCT with low PNa/PCl and falls progressively to zero in JM PCT with high PNa/PCl. From these data we conclude that anion concentration gradients drive an important diffusive flux of sodium chloride through the paracellular pathway only in PCT with low PNa/PCl ratios.
Animals↗
Relative sodium-to-chloride permeability in the proximal convoluted tubule.
Electrophysiological techniques were used in isolated perfused proximal convoluted tubules (PCT) to examine the effect of changes in bath protein concentration on paracellular properties and of active salt transport on relative sodium-to-chloride permeability (PNa/PCl). Control transepithelial potential difference (PD) and NaCl dilution potentials were determined in tubules perfused and bathed with an ultrafiltrate-like solution. PNa/PCl was calculated from the NaCl dilution potential. In the first series of experiments PD and PNa/PCl were redetermined in the same PCT following three experimental maneuvers known to inhibit active salt transport. Addition of 10(-5) M ouabain to the bath, removal of luminal glucose and alanine, and removal of luminal glucose, alanine, bicarbonate, and acetate reduced PD but did not alter the NaCl dilution potential, and therefore PNa/PCl was constant. Constant PNa/PCl in these experiments suggests a) that lowering bath NaCl concentration does not change transcellular current flow, b) that PNa/PCl reflects the ion selectivity of the paracellular pathway, and c) that the ion selectivity of the paracellular pathway is independent of active salt transport. In the second set of experiments PD and PNA/PCl were redetermined following addition of protein to the bath. Neither PD nor PNa/PCl was altered. Analyses of these data argue against modulation of paracellular permeability by bath protein in the in vitro rabbit PCT and suggest that the ion selectivity of the paracellular pathway is determined predominantly by junctional complexes rather than lateral intercellular spaces.
Animals↗
Effects of surgery on plasma volume and salt and water excretion in rats.
Surgical preparation of rats for micropuncture resulted in a marked decrease in sodium excretion (UNaV) compared to awake animals. Associated with surgery, hematocrit (Hct) rose. Studies were performed to determine whether the rise in Hct resulted from reduced plasma volume (PV) or increased red cell volume (RCV) and to explore the relation of such alterations to the fall in UNaV. PV and RCV were determined in the calm awake rat using 125I-albumin and 51Cr-labeled red blood cells. Micropuncture surgery was performed and RCV, PV, and Hct again measured. After anesthesia and femoral artery catheterization, Hct was not different from Hct in awake animals (42.9 +/- 2.8%). The Hct increased following surgery to 48.2 +/- 2.8% (P less than 0.001), accompanied by a large fall in PV (-18.9 +/- 2.3%, P less than 0.001) with no change in RCV. Plasma volume repletion to awake values restored UNaV toward levels appropriate for dietary intake in animals on a high salt diet. Althouth plasma repletion slightly increased UNaV above awake values in low salt diet rats, they continued to avidly retain salt with respect to total salt load.
Anesthesia↗
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.
Absorption↗
Transepithelial potential difference profile of the distal tubule of the rat kidney.
In a recent micropuncture study electrodes with relatively large tips (3 to 5 mu O.D.) and, hence, low tip resistances were used to measure the transepithelial potential difference (PD) across the proximal tubule of the rat kidney. The present study reexamines the PD of the distal tubule of the rat kidney using such electrodes. In contrast to previous studies where a negative PD has been uniformly found in the distal tubule, the transtubular PD was found to be positively oriented (+3.7 mv) when particular efforts were made to puncture the earliest accessible segments. In accord with previous observations, the PD of the late segment was consistently negative (mean, -19.6 mv). Morphologic examination of the epithelium at the site of puncture suggests that in the very early distal tubule where positive potentials are recorded, the epithelium is characteristic of the distal convoluted tubule. By contrast, in the latter part of the distal tubule, where negative potentials are recorded, the epithelium displays the morphologic characteristics of the cortical collecting duct. The results of these studies suggest that the net transport properties of the distal tubule, that is the region of the nephron beginning just beyond the macula densa and extending to the first junction with another renal tubule, are a composite of activities of at least two types of epithelium.
Animals↗