Depressed distal tubule acidification corrects chloride-deplete alkalosis in rats

1990 ◽  
Vol 259 (4) ◽  
pp. F636-F644 ◽  
Author(s):  
D. E. Wesson
Keyword(s):  
Linear Regression ◽  
Proximal Tubule ◽  
Metabolic Alkalosis ◽  
Wistar Rats ◽  
Distal Tubule ◽  
Bicarbonate Reabsorption ◽  
Dependent Relationship ◽  
Distal Tubules ◽  
Lower Slope ◽  
Filtered Load

We investigated the relative contributions made by the proximal and distal tubule to the correction of Cl-deplete metabolic alkalosis induced by systemic administration of NaCl. Free-flow micropuncture was used to examine net bicarbonate reabsorption in superficial proximal and distal tubules of anesthetized Munich-Wistar rats during maintenance and correction of chronic furosemide-induced Cl-deplete metabolic alkalosis. The distal tubule of animals with correcting vs. maintained alkalosis had a lower fractional reabsorption of bicarbonate (38 vs. 75%, P less than 0.001) and a lower slope of the linear regression comparing absorption to delivered load (0.48 vs. 0.99, P less than 0.02). By contrast, proximal tubule of animals with correcting vs. maintained alkalosis had fractional reabsorption (85 vs. 90%, P = 0.07) and slopes of the regression comparing reabsorption to filtered load (1.09 vs. 0.98, P = 0.48) that were not different. The data indicate that correction of Cl-deplete metabolic alkalosis induced by NaCl administration involves a qualitative decreased in bicarbonate reabsorption in distal tubule with maintenance of the same load-dependent relationship for bicarbonate reabsorption in proximal tubule.

Distal tubule unidirectional HCO3 reabsorption in vivo during acute and chronic metabolic alkalosis in the rat

1994 ◽  
Vol 266 (6) ◽  
pp. F919-F925 ◽  
Author(s):  
D. Z. Levine ◽  
M. Iacovitti ◽  
S. Buckman ◽  
D. Vandorpe ◽  
V. Harrison ◽  
...  
Keyword(s):  
Metabolic Alkalosis ◽  
Distal Tubule ◽  
Bicarbonate Secretion ◽  
Bafilomycin A1 ◽  
Secretory Phase ◽  
Plasma Bicarbonate ◽  
Bicarbonate Reabsorption ◽  
Chloride Depletion ◽  
Distal Tubules

During metabolic alkalosis (MA) associated with 2 days of dietary chloride restriction, there is net bicarbonate secretion by rat distal tubules in vivo, whereas after 5 wk of chloride depletion alkalosis there is net bicarbonate reabsorption. To examine unidirectional components of net bicarbonate reabsorption during chronic MA, we measured distal tubule unidirectional bicarbonate secretion (Jsec) and reabsorption (Jreab), as well as the inhibitor sensitivity of Jreab. In control, 2-day, and 7-day alkalosis, Jsec was similar. Jreab, however, was only present in 7-day MA (17 +/- 3 pmol.min-1.mm-1, P < 0.05). This Jreab was completely suppressed by perfusion with 10(-7) M bafilomycin A1, partially suppressed with 10(-5) M Schering (Sch)-28080 (4 +/- 2 pmol.min-1.mm-1, P < 0.1), and converted into a secretory flux by 3 mM amiloride. We conclude that adaptation to chloride depletion MA from the acute secretory phase to the chronic state, where plasma bicarbonate is sustained at elevated levels, does not involve suppression of distal tubule Jsec but rather enhanced Jreab, which is sensitive to bafilomycin, Sch-28080, and amiloride.

scholarly journals The mechanism of bicarbonate reabsorption in the proximal and distal tubules of the kidney. 1965.

1998 ◽  
Vol 9 (6) ◽  
pp. 1134-1145
Author(s):  
F C Rector ◽  
N W Carter ◽  
D W Seldin
Keyword(s):  
Steady State ◽  
Carbonic Anhydrase ◽  
Proximal Tubule ◽  
Intravenous Injection ◽  
Distal Tubule ◽  
Ph Sensitive ◽  
Tubular Cells ◽  
Bicarbonate Reabsorption ◽  
Luminal Membrane ◽  
Distal Tubules

The mechanism of HCO3- reabsorption in proximal and distal tubules was examined in rats undergoing NaHCO3 diuresis. The steady-state intratubular pH was measured with pH-sensitive glass microelectrodes and compared with the equilibrium pH calculated from the HCO3- concentration of the tubular fluid (measured with quinhydrone electrodes) and plasma Pco2. In the proximal tubule the intratubular pH and the equilibrium pH were identical, indicating no accumulation of excess H2CO3. After inhibition of carbonic anhydrase, however, intratubular pH was significantly lower (0.85 pH U) than the equilibrium pH. It was concluded that HCO3- reabsorption in the proximal tubule was mediated by H+ secretion, but that carbonic anhydrase located in the luminal membrane of the cell prevented H2CO3 from accumulating in the tubular fluid. In the distal tubule the intratubular pH was 0.85 U lower than the equilibrium pH. This difference could be obliterated by an intravenous injection of carbonic anhydrase. It was concluded that HCO3- reabsorption in this segment was also accomplished by H+ secretion. The accumulation of excess H2CO3 in the tubular fluid indicated that, in contrast to the proximal tubule, carbonic anhydrase was not located in the luminal membrane of distal tubular cells.

Mechanism of acidification along cortical distal tubule of the rat

1994 ◽  
Vol 266 (2) ◽  
pp. F218-F226 ◽  
Author(s):  
R. Fernandez ◽  
M. J. Lopes ◽  
R. F. de Lira ◽  
W. F. Dantas ◽  
E. J. Cragoe Junior ◽  
...  
Keyword(s):  
Channel Blocker ◽  
Exchange Resin ◽  
Rat Kidney ◽  
Specific Inhibitor ◽  
Distal Tubule ◽  
Ringer Solution ◽  
Na Channel ◽  
Bafilomycin A1 ◽  
Bicarbonate Reabsorption ◽  
Distal Tubules

The cellular mechanism of luminal acidification (bicarbonate reabsorption) was studied in cortical distal tubules of rat kidney. The stopped-flow microperfusion technique was applied to early distal (ED) and late distal (LD) segments, perfused with bicarbonate Ringer solution to which specific inhibitors were added, to measure bicarbonate reabsorption [HCO3 flux (JHCO3)]. pH and transepithelial potential difference (Vt) were recorded by double-barreled H+ exchange resin/reference (1 M KCl) electrodes. Amiloride increased stationary pH and reduced Vt in both early and late segments. Hexamethylene-amiloride (HMA), a specific Na(+)-H+ exchange blocker, reduced JHCO3 in both segments (ED by 43.6 and LD by 40.3%) without affecting Vt. Benzamil, an Na(+)-channel blocker, reduced Vt by 75.9 in ED and 74.9% in LD but had no significant effect on acidification in both segments. The specific inhibitor of H(+)-ATPase, bafilomycin A1, inhibited LD JHCO3 at a concentration of 2 x 10(-7) M by 49%, but ED was inhibited by 24% only at 2 x 10(-6) M. Sch-28080, an inhibitor of gastric H(+)-K(+)-ATPase, reduced JHCO3 by 35% in LD of K(+)-depleted rats but not in control rats and had no effect on ED. These data indicate that, in ED, bicarbonate reabsorption is mediated mostly by Na(+)-H+ exchange. In LD, there is evidence for contribution of Na(+)-H+ exchange, vacuolar H(+)-ATPase, and H(+)-K(+)-ATPase (in K(+)-depleted rats) to bicarbonate reabsorption.

Effects of acid-base disturbances on renal handling of magnesium in the dog

1986 ◽  
Vol 70 (3) ◽  
pp. 277-284 ◽  
Author(s):  
Norman L. M. Wong ◽  
Gary A. Quamme ◽  
John H. Dirks
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Indirect Effect ◽  
Metabolic Alkalosis ◽  
Distal Tubule ◽  
Acid Base ◽  
Renal Handling ◽  
Chronic Metabolic Acidosis ◽  
Magnesium Transport

1. Clearance and micropuncture studies were performed in four groups of acutely thyropara-thyroidectomized animals to study the effects of alkalosis and acidosis on the renal handling of magnesium. 2. Our results indicate that chronic metabolic acidosis reduces, whereas acute metabolic alkalosis enhances, magnesium reabsorption. 3. The site within the nephron where absorption of magnesium increases or decreases during acid-base disturbances was beyond the late proximal tubule. 4. Tubular fluid bicarbonate was also measured in these experiments, and the results indicated that magnesium reabsorption in the distal tubule correlated to bicarbonate delivery. However, whether this was a direct or an indirect effect of bicarbonate on magnesium transport could not be delineated.

High affinity Ca2+–Mg2+ ATPase in the distal tubule of the mouse kidney

1987 ◽  
Vol 65 (10) ◽  
pp. 2093-2098 ◽  
Author(s):  
Michèle G. Brunette ◽  
Sylvie Blouin ◽  
Meathan Chan
Keyword(s):  
Proximal Tubule ◽  
Kinetic Parameters ◽  
Atp Hydrolysis ◽  
Limit Of Detection ◽  
Distal Tubule ◽  
Mouse Kidney ◽  
Distal Nephron ◽  
Low Concentrations ◽  
Distal Tubules ◽  
Shed Light

The purpose of this study was to investigate whether Ca2+–Mg2+ ATPase in the distal tubule (where calcium transport is active, against a gradient, and hormone dependent) presents some characteristics different from those observed in the proximal tubule, and whether these characteristics are likely to shed light on the respective roles of this enzyme at the two sites of the nephron. The Ca2+- and Mg2+-dependent ATP hydrolysis was measured in microdissected segments of the distal nephron, the kinetic parameters were determined, and the influence of magnesium upon the sensitivity to calcium was examined. Results were compared with those obtained in the proximal tubule, and in purified membranes as reported by others. In the distal tubule, low concentrations of Mg2+ (< 10−7 M) did not influence ATP hydrolysis. At concentrations above 10−7 M, Mg2+ increased ATP hydrolysis according to Michaelis kinetics (apparent Km = 11.3 ± 2.4 μM, Vmax = 219 ± 26 pmol∙mm−1∙20 min−1). The addition of 1 μM Ca2+ decreased the apparent Km for Mg2+ and the Vmax for Mg2+. Similar results were obtained in the proximal tubule. At low Mg2+ concentrations, Ca2+ also stimulated ATP hydrolysis according to Michaelis kinetics with an apparent Km value for Ca2+ of 0.18 ± 0.06 and 0.10 ± 0.03 μM Ca2+ (ns) and a Vmax of 101 ± 12 and 89 ± 9 pmol∙mm−1∙20 min−1 (ns) in the distal and proximal tubules, respectively. In the two segments, the addition of Mg2+ strongly decreased the sensitivity to 1 μM Ca2+ so that at 1 mM Mg2+, the Ca2+-dependent ATPase activity was at the limit of detection. In conclusion, the kinetic parameters of the Ca2+- and Mg2+-dependent ATP hydrolysis were similar at the two sites of the nephron, and were also similar to those reported for the enzyme present in purified basolateral membranes. The nonadditive effect of the two cations Ca2+ and Mg2+ suggests that the two ATPase activities belong to the same enzyme, and this enzyme is the same in the proximal and distal tubules. Differences in Ca2+ transport characteristics should be attributed to factors other than variations in the nature of the Ca2+–Mg2+ ATPase.

scholarly journals Endopeptidases (kininases) are able to hydrolyze kinins in tubular fluid along the rat nephron

1999 ◽  
Vol 277 (1) ◽  
pp. F66-F74 ◽  
Author(s):  
D. E. Casarini ◽  
M. A. Boim ◽  
R. C. R. Stella ◽  
N. Schor
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Proximal Tubule ◽  
Physiological Role ◽  
Distal Tubule ◽  
Neutral Endopeptidase ◽  
Prolyl Endopeptidase ◽  
Proximal Tubules ◽  
Converting Enzyme ◽  
Distal Nephron ◽  
Distal Tubules

The activities of serine endopeptidase, prolyl endopeptidase and neutral endopeptidase were determined in tubular fluid collected from several portions of the rat nephron as well as in urine. The enzyme activities were measured by HPLC using bradykinin (BK) as substrate. Free residual peptides of BK obtained by the action of these enzymes on the locally produced BK were also determined. The endopeptidase activities were found to be present throughout the nephron. Equimolar fragments of BK were detected in the early proximal tubule (Arg1-Pro7, Phe8-Arg9, Arg1-Gly4, Phe5-Arg9, and BK), late proximal tubule (Arg1-Phe5, Arg1-Pro7, Gly4-Pro7, Gly4-Arg9, and BK), late distal tubule (Arg1-Gly4, Phe5-Arg9, Arg1-Phe5, Ser6-Arg9, Gly4-Arg9, BK, and [des-Arg9]BK) and urine (Phe8-Arg9, Phe5-Arg9, Arg1-Phe5, Ser6-Arg9, Arg1-Pro7, Gly4-Pro7, Gly4-Arg9, BK, and [des-Arg9]BK). Our data suggest that the endopeptidases and exopeptidases are secreted by the nephron. Early proximal tubules secrete angiotensin converting enzyme and neutral endopeptidase, differing from late distal tubules that produce prolyl endopeptidase, serine endopeptidase, carboxypeptidase, and also neutral endopeptidase. All enzymes detected along the rat nephron were found in the urine. The existence of endopeptidases and carboxypeptidase in the distal nephron may have a potential physiological role in the inactivation of the kinins formed by kallikrein in the kidney and also in the inactivation of additional peptides other than BK.

In vivo adaptation of bicarbonate reabsorption by rat distal tubules during acid loading

1994 ◽  
Vol 267 (5) ◽  
pp. F737-F747 ◽  
Author(s):  
D. Z. Levine ◽  
M. Iacovitti ◽  
S. Buckman ◽  
D. Vandorpe ◽  
V. Harrison ◽  
...  
Keyword(s):  
Water Flux ◽  
Distal Tubule ◽  
Bafilomycin A1 ◽  
Bicarbonate Reabsorption ◽  
Distal Tubules ◽  
Acid Loading ◽  
Fasted Rats ◽  
Predominant Effect ◽  
Stimulation Of

We carried out in vivo microperfusion experiments in acid-loaded rats to characterize the adaptive response of the unidirectional components secretory flux (Jsec) and reabsorptive flux (Jreab)] of distal tubule bicarbonate reabsorption and to test the hypothesis that Jreab is dependent on bafilomycin A1-sensitive H(+)-adenosinetriphosphatase activity. During 18 h of severe acidosis there was a significant decrease in Jsec (-15 +/- 3 vs. -38 +/- 5 pmol.min-1.mm-1, P < 0.05) and a significant increase in Jreab (37 +/- 6 vs. 0 +/- 5 pmol.min-1.mm-1, P < 0.05), which was insensitive to 10(-5) M bafilomycin A1, 10(-5) M Sch-28080, and 3 mM amiloride. After 3 days of acid loading, these same inhibitors reduced Jreab by approximately 60%. However, when water flux was completely inhibited by isosmotic perfusion, a significant Jreab (15 +/- 2 pmol.min-1.mm-1) resistant to 10(-5) M bafilomycin A1 persisted, as in severe acidosis. In reabsorbing distal tubules of overnight-fasted rats, Sch-28080 elicited no inhibition, whereas bafilomycin A1 and amiloride had significant effects (28 +/- 5, 24 +/- 4, respectively, vs. 50 +/- 4 pmol.min-1.mm-1 for fasted rats, P < 0.05). Thus, although Jsec is reduced in the transition from mild to severe metabolic acidosis of 18-h duration, the predominant effect is a stimulation of bafilomycin A1-resistant Jreab.

Bicarbonate reabsorption by the kidney of the newborn rabbit

1989 ◽  
Vol 256 (1) ◽  
pp. F29-F34
Author(s):  
A. J. van der Heijden ◽  
J. P. Guignard
Keyword(s):  
Metabolic Alkalosis ◽  
Filtration Rate ◽  
Animal Species ◽  
Carbon Dioxide Tension ◽  
Acid Base ◽  
Renal Handling ◽  
Newborn Rabbit ◽  
Bicarbonate Reabsorption ◽  
Filtered Load ◽  
Reabsorption Rate

Bicarbonate reabsorption by the immature kidney in response to acute acid-base changes was assessed in 50 anesthetized newborn rabbits before the end of nephrogenesis. The normal newborn rabbit (age 5-12 days) is in a state of hypochloremic metabolic alkalosis (PHCO3-, 31.9 +/- 0.6 mmol/l; PCl-, 83.1 +/- 1.0) and excretes a hypertonic (Uosmol = 578 +/- 41 mosmol/kgH2O), alkaline (UpH = 7.40 +/- 0.15) urine containing 50 +/- 9 mmol/l Cl- and 13 +/- 4 mmol/l Na+. The alkalosis is probably generated by an alkaline load contained in the mother's milk and maintained by a state of chloride wasting and volume contraction. In this alkalotic model, bicarbonate reabsorption, expressed per milliliter glomerular filtration rate (GFR), correlates positively with arterial CO2 pressure (PaCO2). The ability of the immature kidney to reclaim filtered bicarbonate in response to an elevation of the plasma carbon dioxide tension remains unlimited up to PaCO2 of 110 mmHg (y = 20.7 + 0.15 x, r = 0.82, P less than 0.001). Hypercapnia is associated with a marked fall in GFR, so that the positive correlation between bicarbonate reabsorption and PaCO2 vanishes when the bicarbonate reabsorption rate is expressed in absolute terms. Bicarbonate reabsorption is strongly dependent on the filtered load during both acutely induced metabolic acidosis and alkalosis. The acid-base state of the newborn rabbit is in sharp contrast with that of most animal species, and the renal handling of bicarbonate as a function of GFR does not show signs of tubular immaturity.

Metabolic acidosis stimulates bicarbonate reabsorption in the early proximal tubule

1989 ◽  
Vol 257 (1) ◽  
pp. F35-F42 ◽  
Author(s):  
R. N. Santella ◽  
F. J. Gennari ◽  
D. A. Maddox
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Plasma Expansion ◽  
Plasma Volume Expansion ◽  
Major Site ◽  
Chronic Metabolic Acidosis ◽  
Bicarbonate Reabsorption ◽  
Filtered Load ◽  
Stimulation Of ◽  
Early Proximal Tubule

The early proximal tubule is the major site for renal bicarbonate reabsorption but little is known about the influence of acidosis on transport in this segment. This study examined early proximal bicarbonate reabsorption in rats with chronic metabolic acidosis (MA) (induced by NH4Cl administration). Rats were studied by free-flow micropuncture techniques, after varying degrees of plasma volume expansion to vary the filtered load of bicarbonate (FLHCO3). At FLHCO3 less than 700 pmol/min, both control and acidotic animals reabsorbed greater than 80% of the filtered load by 2 mm from Bowman's space. At higher FLHCO3 (700–1,100 pmol/min), reabsorption in the early proximal tubule was significantly greater in MA rats vs. control (633 +/- 26 vs. 449 +/- 24 pmol/min, between 1 and 2 mm from Bowman's space, P less than 0.001). This MA-induced stimulation of early proximal bicarbonate reabsorption was completely reversed by restoring systemic pH to normal either by acute hypocapnia or alkali infusion. Thus bicarbonate reabsorption in the early proximal tubule correlated closely with changes in systemic pH in rats with MA when bicarbonate delivery was increased by plasma expansion. The mechanism of this effect remains to be determined.

Determination of disequilibrium pH in the rat kidney in vivo: evidence of hydrogen secretion

1981 ◽  
Vol 240 (2) ◽  
pp. F138-F146 ◽  
Author(s):  
T. D. DuBose ◽  
L. R. Pucacco ◽  
N. W. Carter
Keyword(s):  
Carbonic Anhydrase ◽  
Metabolic Alkalosis ◽  
Rat Kidney ◽  
Respiratory Acidosis ◽  
Distal Tubule ◽  
Distal Nephron ◽  
Bicarbonate Reabsorption ◽  
Disequilibrium Ph ◽  
Tubule Fluid

The recent demonstration of elevated PCO2 in structures of the rat renal cortex indicated that previous determinations of disequilibrium pH (pHDq), and thus the differentiation of H+ secretion from bicarbonate reabsorption per se, required further evaluation. A new aspiration pH electrode was developed to allow tubule fluid to achieve chemical equilibrium at the PCO2 prevailing in vivo. In control and bicarbonate-loaded rats a pHDq was not observed in either proximal or distal tubules. After intravenous benzolamide a significant acid pHDq was observed in the proximal (but not the distal) nephron, and increased further during metabolic alkalosis. During combined metabolic alkalosis and respiratory acidosis a significant pHDq was present in the distal but not in the proximal tubule. Aldosterone administration to bicarbonate-loaded, hypercapnic rats did not alter the distal pHDq further. When present, the pHDq in the distal tubule was obliterated by carbonic anhydrase infusion. We conclude that proximal but not distal tubule fluid is in functional contact with carbonic anhydrase; the enzyme is in excess in the proximal lumen and H2CO3 did not accumulate even during conditions associated with increased H+ secretion; the basal rate of H+ secretion in the distal nephron accessible to cortical micropuncture is less than previously assumed. The data support the view that H+ secretion is the major mechanism of renal bicarbonate reabsorption.

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