Effect of carbonic anhydrase inhibition on proximal tubular bicarbonate reabsorption

1963 ◽  
Vol 205 (4) ◽  
pp. 693-696 ◽  
Author(s):  
James R. Clapp ◽  
John F. Watson ◽  
Robert W. Berliner
Keyword(s):  
Carbonic Anhydrase ◽  
Proximal Tubule ◽  
Intravenous Administration ◽  
Distal Portion ◽  
Bicarbonate Concentration ◽  
Plasma Bicarbonate ◽  
Bicarbonate Reabsorption ◽  
Carbonic Anhydrase Inhibition ◽  
Before And After ◽  
Proximal Tubular

Samples of fluid from the proximal tubule were collected for the measurement of pH and bicarbonate concentration before and after the administration of acetazolamide (Diamox). Samples collected before acetazolamide were consistently more acid than plasma with the most acid samples coming from the more distal portion of the proximal tubule. After the intravenous administration of acetazolamide, the pH and bicarbonate concentration were consistently higher than in plasma. Bicarbonate concentrations as high as 2.8 times that in plasma were observed. The rise in proximal tubular fluid bicarbonate concentration after acetazolamide is presumably due to a reduction in the rate of bicarbonate reabsorption out of proportion to any impairment in proximal tubular fluid volume reduction.

Maleate-induced bicarbonaturia in the dog: a carbonic anhydrase-independene effect

1976 ◽  
Vol 231 (4) ◽  
pp. 1010-1017 ◽  
Author(s):  
A Gougoux ◽  
G Lemieux ◽  
N Lavoie
Keyword(s):  
Carbonic Anhydrase ◽  
Intravenous Administration ◽  
Maleic Acid ◽  
Krebs Cycle ◽  
Urinary Ph ◽  
Renal Effects ◽  
Carbonic Anhydrase Inhibition ◽  
Tubular Lumen ◽  
Proximal Tubular ◽  
Anesthetized Dogs

Studies were performed to characterize the renal effects of maleate in anesthetized dogs. Following the intravenous administration of maleate or maleic acid (50 mg/kg), mean fractional bicarbonate excretion (CHCO3/GFR) rose to as high as 26%. Na, K, and phosphate excretion also increased markedly, whereas C1 excretion remained low. An initial transient fall in urinary pH from 6.53 to 6.13 contrasted sharply with the rapid alkalinization of the urine induced by acetazolamide administration. During saline expansion CHCO3/GFR rose from 4 to 37% after maleate administration, whereas Cl excretion did not change significantly. During continuous carbonic anhydrase inhibition with acetazolamide, maleate administration resulted in a further rise in CHCO3/GFR from 22 to 35%. Whereas CPO4/GFR increased only from 1 to 3% during acetazolamide administration, this ratio reached 75% following the addition of maleate. Fumarate, the transisomer of maleate, and malonate, a well-known inhibitor of Krebs cycle, failed to affect bicarbonate excretion. This study demonstrates that maleate inhibits the fraction of bicarbonate reabsorption uncatalyzed by carbonic anhydrase. Impaired anionic reabsorption of bicarbonate or accelerated passive backflux of this ion into proximal tubular lumen are the two mechanisms that best explain the bicarbonaturia induced by maleate.

Relative effects of systemic pH, PCO2, and bicarbonate concentration on ileal ion transport

1983 ◽  
Vol 245 (2) ◽  
pp. G230-G235 ◽  
Author(s):  
A. N. Charney ◽  
L. P. Haskell
Keyword(s):  
Exchange Process ◽  
Respiratory Acidosis ◽  
Electrolyte Transport ◽  
Sodium Absorption ◽  
Sprague Dawley ◽  
Bicarbonate Concentration ◽  
In Situ Perfusion ◽  
Plasma Bicarbonate ◽  
Blood Ph ◽  
Before And After

To determine the relative effects of systemic pH, CO2 tension (PCO2), and bicarbonate concentration on ileal electrolyte transport, states of acute metabolic acidosis and alkalosis were created in Sprague-Dawley rats by gavage feeding (NH4)2SO4 and NaHCO3, respectively. During in situ perfusion of the ileum in anesthetized animals, electrolyte transport was measured before and after respiratory compensation of the systemic pH. Acute respiratory acidosis and alkalosis also were studied by ventilating animals with 0, 3, or 8% CO2. When animals in all groups were considered, net sodium absorption correlated very well with blood pH (r = -0.97). Net bicarbonate secretion correlated with the plasma bicarbonate concentration (r = 0.91) independently of blood pH and PCO2. Net chloride absorption correlated with blood PCO2 (r = 0.92) and was altered when systemic pH and bicarbonate concentration changed in opposite directions. Alterations in luminal pH and PCO2 did not affect electrolyte transport. These results suggest that systemic pH affects a sodium chloride absorptive process and that the plasma bicarbonate concentration affects a chloride absorptive-bicarbonate secretory exchange process in the rat ileum.

Osmolality, bicarbonate concentration, and water reabsorption in proximal tubule of the dog nephron

1963 ◽  
Vol 205 (2) ◽  
pp. 273-280 ◽  
Author(s):  
James R. Clapp ◽  
John F. Watson ◽  
Robert W. Berliner
Keyword(s):  
Plasma Concentration ◽  
Proximal Tubule ◽  
Proximal Convoluted Tubule ◽  
Water Reabsorption ◽  
Bicarbonate Concentration ◽  
Water Diuresis ◽  
Vasopressin Infusion ◽  
Proximal Tubular

Micropuncture and microanalytical techniques were used to study the effect of antidiuresis and water diuresis on osmolality, bicarbonate concentration, and water reabsorption in the proximal tubule of the dog nephron. Samples collected during antidiuresis and water diuresis remained isotonic to plasma throughout the first 50% of the proximal convoluted tubule. Mean bicarbonate concentrations of 16 mEq/liter and 17 mEq/liter were found in the middle third of the tubule during antidiuresis and water diuresis, respectively. These values were slightly less than the plasma concentration of 22 mEq/liter. Proximal tubular fluid samples for inulin concentration were collected during antidiuresis, water diuresis, and during vasopressin infusion in water-loaded dogs. A mean tubular fluid to plasma (TF/P) inulin ratio of 2.3 was found in the middle third of the proximal tubule during antidiuresis. This value is significantly different ( P < 0.01) from a mean of 1.6 in the same portion of the tubule during water diuresis. Vasopressin administration to hydrated dogs returned the TF/P inulin ratio in the middle third of the proximal tubule to 2.0. These results suggest that vasopressin stimulated Na reabsorption in the proximal tubule of the dog nephron.

Single proximal tubules of Necturus kidney. VIII: Na and K determinations by glass electrodes

1963 ◽  
Vol 204 (5) ◽  
pp. 743-748 ◽  
Author(s):  
Raja N. Khuri ◽  
David A. Goldstein ◽  
David L. Maude ◽  
Charles Edmonds ◽  
A. K. Solomon
Keyword(s):  
Proximal Tubule ◽  
Distal Portion ◽  
Proximal Tubules ◽  
Living Animal ◽  
Flame Photometer ◽  
Proximal Tubular ◽  
Glass Electrodes ◽  
K Concentration

Cation-sensitive glass electrodes have been used to measure Na and K concentrations in Necturus serum and in glomerular and proximal tubular fluid from Necturus kidney. It has been found that the ratio [Na]glomerulus/[Na]serum is 1.00 ± 0.02 and the ratio [Na]tubule/[Na]glomerulus is 0.99 ± 0.01 thus confirming previous measurements with the flame photometer which indicated that tubular Na concentration did not change as fluid moved along the proximal tubule in Necturus kidney. These results were also confirmed with cation electrodes placed in situ in the living animal. The K concentration in fluid collected from the most distal portion of the proximal tubule was found to be 1.8 ± 0.1 times more concentrated than that in the glomerulus, in agreement with a ratio of 1.6 ± 0.1 previously obtained on the basis of flame photometer measurements by Oken and Solomon.

Evidence that parallel Na+-H+ and Cl(-)-HCO3-(OH-) antiporters transport NaCl in the proximal tubule

1987 ◽  
Vol 252 (2) ◽  
pp. F338-F345 ◽  
Author(s):  
M. Baum
Keyword(s):  
Carbonic Anhydrase ◽  
Proximal Tubule ◽  
Driving Forces ◽  
Disulfonic Acid ◽  
Albumin Solution ◽  
Nacl Transport ◽  
Volume Absorption ◽  
Proximal Tubular ◽  
High Chloride

The present in vitro microperfusion study examined whether active NaCl transport in the proximal convoluted tubule (PCT) occurs via parallel Na+-H+ and Cl(-)-HCO3-(OH-) exchangers. PCT were perfused with a high-chloride, low-bicarbonate solution simulating late proximal tubular fluid, and were bathed in a similar solution containing 6 g/dl albumin. In this setting the driving forces responsible for passive NaCl transport are eliminated. Addition of 0.1 or 0.5 mM luminal 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), 0.5 mM luminal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), or 0.1 mM bath ethoxyzolamide, a lipophilic carbonic anhydrase inhibitor, resulted in an approximately 50% reduction in volume absorption. Inhibition of the Na+-H+ antiporter with 1.0 mM luminal amiloride inhibited volume absorption by 50%. The transepithelial potential difference (PD) was not significantly different from zero, consistent with an electroneutral mechanism for active NaCl transport. The effect of a Cl(-)-HCO3-(OH-) exchanger on acidification was examined in PCT perfused with an ultrafiltrate-like solution and bathed in a serumlike albumin solution. Addition of 0.5 mM DIDS did not significantly decrease volume absorption, demonstrating that luminal DIDS did not result in a nonspecific decrease in solute transport. Luminal DIDS significantly stimulated bicarbonate absorption, consistent with a Na+-H+ antiporter running in parallel with a Cl(-)-HCO3-(OH-) antiporter, which exchanges luminal Cl- for cellular HCO3- (or OH-). In conclusion, these data are consistent with parallel Na+-H+ and Cl(-)-HCO3-(OH-) antiporters mediating neutral active NaCl transport in the PCT.

A model of proximal tubular bicarbonate absorption

1985 ◽  
Vol 248 (2) ◽  
pp. F272-F281 ◽  
Author(s):  
R. J. Alpern ◽  
F. C. Rector
Keyword(s):  
Extracellular Fluid ◽  
High Plasma ◽  
Bicarbonate Concentration ◽  
Solvent Interactions ◽  
Proton Secretion ◽  
Plasma Bicarbonate ◽  
Flow Dependence ◽  
Model Predictions ◽  
Proximal Tubular ◽  
Luminal Flow

A model is presented that utilizes determinants of acidification defined from microperfusion studies in the rat to stimulate the effect on absolute bicarbonate absorption along the entire proximal convoluted tubule. Net bicarbonate absorption is considered to consist of active transcellular proton secretion in parallel with passive paracellular bicarbonate diffusion. The rate of proton secretion is calculated as a function of luminal bicarbonate concentration using Michaelis-Menten kinetics. The K1/2 is modified by luminal flow rate and the Vmax by peritubular bicarbonate concentration. Solute-solvent interactions and axial heterogeneity are also included as determinants of proton secretion rate. The model demonstrates that a given percentage stimulation or inhibition of active proton secretion leads to a much smaller effect on absolute proximal bicarbonate absorption along the entire tubular length. This blunting of the stimulation or inhibition is greatest when filtered bicarbonate load is limited by decreases in glomerular filtration rate or plasma bicarbonate concentration. In addition, the model shows that flow dependence is greater at low plasma bicarbonate concentrations, whereas the effect of extracellular fluid volume expansion is greater at high plasma bicarbonate concentrations. Agreement between the model predictions and the results of free-flow micropuncture studies from our laboratory is good with the exception of the effect of raising plasma bicarbonate concentration. This discrepancy is resolvable by allowing the effect of peritubular pH to increase along the length of the tubule, a hypothesis that requires verification.

Glomerular-tubular balance for bicarbonate in the dog

1975 ◽  
Vol 228 (1) ◽  
pp. 98-106 ◽  
Author(s):  
CM Bennett ◽  
PD Springberg ◽  
NR Falkinburg
Keyword(s):  
Functional Relationship ◽  
Potassium Concentration ◽  
Extracellular Fluid ◽  
High Protein Diet ◽  
Plasma Potassium ◽  
Absolute Rate ◽  
Bicarbonate Concentration ◽  
Plasma Bicarbonate ◽  
Bicarbonate Reabsorption ◽  
The Absolute

Previous work that apparently showed a functional relationship between GFR and maximum bicarbonate reabsorption was done at a time when the effects on the latter of several factors (PCO2, plasma potassium concentration, and extracellular fluid volume expansion) were not recognized. The present study re-examines this relationship, while controlling these factors. In 14 hydropenic dogs, bicarbonate reabsorption per unt GFR increased linearly with increases in plasma bicarbonate concentration. At any level of plasma bicarbonate concentration,the absolute rate of bicarbonate reabsorption was functionally related to the GFR. In six volume-expanded dogs, bicarbonate reabsorption remained stable at 20-22 mmol/liter GFR as plasma bicarbonate was raised to greater than 40mM. The absolute rate of bicarbonate reabsorption increased with large increases in GFR induced by methylprednisolone and high-protein diet. In a third group of dogs, bicarbonate reabsorption varied directly with increases in GFR, while plasma bicarbonate concentration was held relatively constant above the threshold. We conclude there is a close functional relationship between the absolute rate of bicarbonate reabsorption and GFR in individual dogs.

Effect of carbonic anhydrase inhibition on mixed venous CO2 tension in anesthetized dogs

1960 ◽  
Vol 15 (3) ◽  
pp. 390-392 ◽  
Author(s):  
Stephen M. Cain ◽  
Arthur B. Otis
Keyword(s):  
Carbonic Anhydrase ◽  
Venous Blood ◽  
Carbonic Anhydrase Inhibitor ◽  
Mixed Venous Blood ◽  
Bicarbonate Concentration ◽  
Significant Difference ◽  
Carbonic Anhydrase Inhibition ◽  
Anesthetized Dogs ◽  
The Difference ◽  
Mixed Venous

The ventilation of one lung in dogs was isolated and that lung continually rebreathed into a small rubber bag. The Pco2 of a sample of the gas in the rebreathing bag was compared with the Pco2 calculated from pH and bicarbonate concentration determined in a sample of mixed venous blood drawn simultaneously. Before the injection of a carbonic anhydrase inhibitor, acetazolamide, the difference between the two values for Pco2 was not significant. After acetazolamide, a highly significant difference (P < 0.001) was found. Apparently, when carbonic anhydrase was inhibited, the dissolved CO2 of mixed venous blood did not attain equilibrium with bicarbonate by the time the blood entered the lung. Submitted on December 18, 1959

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