Micropuncture Studies of Chloride and Bicarbonate Absorption in the Proximal Renal Tubule of the Rat in Respiratory Acidosis and in Chloride Depletion

1970 ◽  
Vol 38 (3) ◽  
pp. 375-383 ◽  
Author(s):  
Y. Warren ◽  
R. G. Luke ◽  
M. Kashgarian ◽  
H. Levitin
Keyword(s):  
Proximal Tubule ◽  
Respiratory Acidosis ◽  
Maximum Plasma ◽  
Plasma Bicarbonate ◽  
Chloride Depletion ◽  
Chloride Absorption ◽  
Chloride Excretion ◽  
Proximal Tubular ◽  
Plasma Chloride ◽  
Urinary Acid

1. Micropuncture studies of chloride and bicarbonate absorption in the proximal tubule under free flow conditions were performed during exposure to 12% CO2 in air, during recovery from CO2 on a low chloride diet with and without concomitant sodium restriction, and during re-exposure to 12% CO2 in air with continuing chloride restriction. 2. After 3 hr of exposure to CO2 there was a significant increase in the TF/P Cl (ratio of tubular fluid to plasma chloride) in the proximal tubule and a significant increase in urinary chloride excretion with a drop in the plasma chloride. Maximum plasma bicarbonate and TF/P Cl levels were reached at 24 hr with no further increase after 48 hr exposure to CO2. Bicarbonate absorption in the proximal tubule formed a reciprocal pattern to chloride absorption. 3. It is concluded, in conjunction with the accompanying balance experiments of Luke et al. (1970), that a rising TF/P Cl in the proximal tubule correlates with increasing proximal tubular absorption of bicarbonate, a rising plasma bicarbonate, and an increasing urinary acid excretion, but not necessarily with external chloride balance, which is regulated by a more distal site in the nephron. In respiratory acidosis and chloride depletion the TF/P Cl in the proximal tubule reflects the intratubular dynamics which influence bicarbonate absorption.

Effects of Chloride Restriction and Depletion on Acid-Base Balance and Chloride Conservation in the Rat

1970 ◽  
Vol 38 (3) ◽  
pp. 385-396 ◽  
Author(s):  
R. G. Luke ◽  
Y. Warren ◽  
M. Kashgarian ◽  
H. Levitin
Keyword(s):  
Proximal Tubule ◽  
Respiratory Acidosis ◽  
Dietary Sodium ◽  
Acid Excretion ◽  
Acid Base Balance ◽  
Plasma Bicarbonate ◽  
Chloride Depletion ◽  
Plasma Chloride ◽  
Urinary Acid ◽  
Net Acid Excretion

1. In the rat dietary chloride restriction has been shown to cause an elevation of the plasma bicarbonate and urinary net acid excretion, provided dietary sodium is available. Likewise the degree of elevation of plasma bicarbonate during chloride depletion, produced by prior exposure to 8% CO2 for 24 hr, was dependent on whether sodium (as the neutral phosphate) was or was not being ingested. 2. Correction of the hypochloraemia and the elevated plasma bicarbonate following exposure to CO2 and subsequent recovery on a low chloride diet is more complete in the rat than the dog. Evidence is presented that the plasma chloride rises in the rat because of the movement of chloride out of intracellular sites, and that chloride depletion and/or the associated metabolic alkalosis elevates endogenous acid production. 3. Chloride depleted rats were re-exposed to 8% CO2 in air. Renal chloride conservation remained intact. The hypochloraemia and rise in plasma bicarbonate in response to CO2 were not dependent on chloruresis although urinary acid excretion and the rise in serum bicarbonate were inhibited when the plasma chloride did not fall. 4. Consideration of these experiments with the related micropuncture experiments of Warren et al. (1970) suggests that: (a) the intimate relationship between hypochloraemia and the elevation of plasma bicarbonate in respiratory acidosis is related to reciprocal changes in proximal tubular absorption of chloride and bicarbonate; (b) chloride depletion can increase bicarbonate absorption in the proximal tubule and urinary net acid excretion; (c) a rise in TF/P Cl in the proximal tubule does not necessarily correlate with changes in external chloride balance; (d) the distal chloride conserving mechanism is unaffected by rates of sodium or phosphate excretion, exposure to carbon dioxide, or increases in the rate of tubular bicarbonate absorption.

scholarly journals Renal compensation to chronic hypoxic hypercapnia: downregulation of pendrin and adaptation of the proximal tubule

2007 ◽  
Vol 292 (4) ◽  
pp. F1256-F1266 ◽  
Author(s):  
Sophie de Seigneux ◽  
Hans Malte ◽  
Henrik Dimke ◽  
Jørgen Frøkiær ◽  
Søren Nielsen ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Collecting Duct ◽  
Chloride Concentration ◽  
Respiratory Acidosis ◽  
Plasma Bicarbonate ◽  
Arterial Ph ◽  
Collecting Ducts ◽  
Chloride Excretion ◽  
Plasma Chloride

The molecular basis for the renal compensation to respiratory acidosis and specifically the role of pendrin in this condition are unclear. Therefore, we studied the adaptation of the proximal tubule and the collecting duct to respiratory acidosis. Male Wistar-Hannover rats were exposed to either hypercapnia and hypoxia [8% CO2 and 13% O2 (hypercapnic, n = 6) or normal air (controls, n = 6)] in an environmental chamber for 10 days and were killed under the same atmosphere. In hypercapnic rats, arterial pH was lower than controls (7.31 ± 0.01 vs. 7.39 ± 0.01, P = 0.03), blood HCO3− concentration was increased (42 ± 0.9 vs. 32 ± 0.24 mM, P < 0.001), arterial Pco2 was increased (10.76 ± 0.4 vs. 7.20 ± 0.4 kPa, P < 0.001), and plasma chloride concentration was decreased (92.2 ± 0.7 vs. 97.2 ± 0.5 mM, P < 0.001). Plasma aldosterone levels were unchanged. In the proximal tubule, immunoblotting showed an increased expression of sodium/bicarbonate exchanger protein (188 ± 22 vs. 100 ± 11%, P = 0.005), confirmed by immunohistochemistry. Total Na/H exchanger protein expression in the cortex was unchanged by immunoblotting (119 ± 10 vs. 100 ± 11%, P = 0.27) and immunohistochemistry. In the cortex, the abundance of pendrin was decreased (51 ± 9 vs. 100 ± 7%, P = 0.003) by immunoblotting. Immunohistochemistry revealed that this decrease was clear in both cortical collecting ducts (CCDs) and connecting tubules (CNTs). This demonstrates that pendrin expression can be regulated in acidotic animals with no changes in aldosterone levels and no external chloride load. This reduction of pendrin expression may help in redirecting the CNT and CCD toward chloride excretion and bicarbonate reabsorption, contributing to the increased plasma bicarbonate and decreased plasma chloride of chronic respiratory acidosis.

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.

Effect of respiratory acidosis on intracellular pH of the proximal tubule

1986 ◽  
Vol 250 (6) ◽  
pp. F1039-F1045
Author(s):  
B. Trivedi ◽  
R. L. Tannen
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Intracellular Ph ◽  
Chronic Phase ◽  
Respiratory Acidosis ◽  
Glucose Production ◽  
Proximal Tubular ◽  
Acute Metabolic Acidosis ◽  
Urinary Citrate ◽  
Co2 Environment

In contrast to chronic metabolic acidosis, chronic respiratory acidosis does not result in an adaptation in either renal ammonia or glucose production. To examine the possibility that this might be explained by a difference in proximal tubule intracellular pH, the response of two pH-sensitive metabolites, citrate and alpha-ketoglutarate, were assessed. Metabolic acidosis of 3 days duration, induced by drinking 1.5% NH4Cl, significantly reduced urinary citrate excretion (172 to 15 mumol/day) and renal cortical citrate (1.33 to 0.88 mumol/g) and alpha-ketoglutarate (0.90 to 0.46 mumol/g) concentrations in comparison with normal rats. Chronic respiratory acidosis, produced by 3 days in a 10% CO2 environment, lowered systemic pH similar to metabolic acidosis but had no effect on either urinary citrate excretion or renal cortical citrate and alpha-ketoglutarate concentrations. By contrast, acute respiratory acidosis (3, 6, or 24 h duration) reduced urinary citrate excretion and renal cortical citrate and alpha-ketoglutarate concentrations in a fashion similar to acute metabolic acidosis. These data suggest that acute acidosis of either respiratory or metabolic origin lowers the intracellular pH of the proximal tubule. However, when the acid-base abnormality enters the chronic phase, proximal tubular intracellular pH remains low with metabolic acidosis but returns to normal values with respiratory acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Generation and characterization of iPSC-derived renal proximal tubule-like cells with extended stability

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vidya Chandrasekaran ◽  
Giada Carta ◽  
Daniel da Costa Pereira ◽  
Rajinder Gupta ◽  
Cormac Murphy ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Retinoic Acid Receptor ◽  
Renal Proximal Tubule ◽  
Whole Body ◽  
Proper Function ◽  
Genome Wide ◽  
Glomerular Filtrate ◽  
Proximal Tubular ◽  
Induced Pluripotent

AbstractThe renal proximal tubule is responsible for re-absorption of the majority of the glomerular filtrate and its proper function is necessary for whole-body homeostasis. Aging, certain diseases and chemical-induced toxicity are factors that contribute to proximal tubule injury and chronic kidney disease progression. To better understand these processes, it would be advantageous to generate renal tissues from human induced pluripotent stem cells (iPSC). Here, we report the differentiation and characterization of iPSC lines into proximal tubular-like cells (PTL). The protocol is a step wise exposure of small molecules and growth factors, including the GSK3 inhibitor (CHIR99021), the retinoic acid receptor activator (TTNPB), FGF9 and EGF, to drive iPSC to PTL via cell stages representing characteristics of early stages of renal development. Genome-wide RNA sequencing showed that PTL clustered within a kidney phenotype. PTL expressed proximal tubular-specific markers, including megalin (LRP2), showed a polarized phenotype, and were responsive to parathyroid hormone. PTL could take up albumin and exhibited ABCB1 transport activity. The phenotype was stable for up to 7 days and was maintained after passaging. This protocol will form the basis of an optimized strategy for molecular investigations using iPSC derived PTL.

Acid-base balance and plasma composition in the aestivating lungfish (Protopterus)

1977 ◽  
Vol 232 (1) ◽  
pp. R10-R17 ◽  
Author(s):  
R. G. DeLaney ◽  
S. Lahiri ◽  
R. Hamilton ◽  
P. Fishman
Keyword(s):  
Plasma Osmolality ◽  
Respiratory Acidosis ◽  
Electrolyte Balance ◽  
Plasma Composition ◽  
Total Plasma ◽  
Acid Base Balance ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Arterial Ph ◽  
Base Balance

Upon entering into aestivation, Protopterus aethiopicus develops a respiratory acidosis. A slow compensatory increase in plasma bicarbonate suffices only to partially restore arterial pH toward normal. The cessation of water intake from the start of aestivation results in hemoconcentration and marked oliguria. The concentrations of most plasma constituents continue to increase progressively, and the electrolyte ratios change. The increase in urea concentration is disproportionately high for the degree of dehydration and constitutes an increasing fraction of total plasma osmolality. Acid-base and electrolyte balance do not reach a new equilibrium within 1 yr in the cocoon.

Acid-Base Relationships in the Blood of the Toad, Bufo Marinus: I. The Effects of Environmental CO2

1979 ◽  
Vol 82 (1) ◽  
pp. 331-344 ◽  
Author(s):  
R. G. BOUTILIER ◽  
D. J. RANDALL ◽  
G. SHELTON ◽  
D. P. TOEWS
Keyword(s):  
Respiratory Acidosis ◽  
Initial Response ◽  
Untreated Animal ◽  
Abrupt Increase ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Ph Values ◽  
Arterial Blood ◽  
Toad Bufo ◽  
Ambient Co2

An abrupt increase in ambient CO2, resulted in a marked respiratory acidosis which took place within 30 min. During this time there was a considerable reduction in the PCO2. difference between arterial blood and inspired gas caused by an increase in ventilations. Prolonged CO2 exposure (24 h) showed that there was some compensation for the acidosis in that plasma bicarbonate concentrations increased substantially. At the same time, however, the PCO2 of arterial blood always rose so that the net result was usually only a small increase in pH. Upon return to air, the blood was backtitrated along a buffer line elevated above and parallel to that seen during the initial response to hypercapnia. The fall in arterial blood PCO2, during the early stages of recovery often led to pH values higher than those seen in the untreated animal. After 48 h in air, recovery had gone further with PCO2 pH and [HCO3-] levels approaching but rarely reaching the pre-exposure values.

Dissociation of proximal tubular glucose and Na+ reabsorption by amphotericin B

1979 ◽  
Vol 236 (4) ◽  
pp. F392-F397
Author(s):  
P. S. Aronson ◽  
J. P. Hayslett ◽  
M. Kashgarian
Keyword(s):  
Proximal Tubule ◽  
Glucose Uptake ◽  
Amphotericin B ◽  
Membrane Vesicle ◽  
Membrane Vesicles ◽  
Na Transport ◽  
Glucose Reabsorption ◽  
Tubular Lumen ◽  
Proximal Tubular ◽  
Necturus Proximal Tubule

The effect of amphotericin B on glucose and Na+ transport was studied in the Necturus proximal tubule and in microvillus membrane vesicles isolated from the rabbit renal cortex. In the Necturus experiments, the rate constants for disappearance of radiolabeled glucose (kG) and mannitol (kM) from the tubular lumen were determined by stop-flow microperfusion. Saturability and Na+-dependence of glucose reabsorption was confirmed, since kG was reduced by raising intratubular glucose from 1 to 5 mM or by replacing intratubular Na+ with choline. Neither maneuver affected kM. Intratubular amphotericin B (10 microgram/ml), previously shown to stimulate active Na+ reabsorption in the Necturus proximal tubule, inhibited kG with no effect on kM. In the membrane vesicle preparation, amphotericin inhibited the uphill glucose uptake which results from imposing a NaCl gradient from outside to inside, but had no effect on glucose uptake in either the absence of Na+ or in the presence of Na+ when there was no Na+ gradient. Amphotericin B stimulated the uptake of Na+ by the vesicles. The observed dissociation of glucose and Na+ transport by amphotericin B is consistent with the concept that proximal tubular glucose reabsorption is energized by the luminal membrane Na+ gradient and is not directly linked to active Na+ transport per se.

Cyclosporin A and vehicle toxicity in primary cultures of rabbit renal proximal tubule cells

1990 ◽  
Vol 259 (6) ◽  
pp. C897-C903 ◽  
Author(s):  
P. P. Sokol ◽  
L. C. Capodagli ◽  
M. Dixon ◽  
P. D. Holohan ◽  
C. R. Ross ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Cyclosporin A ◽  
Primary Cultures ◽  
Distal Tubule ◽  
Ph Gradient ◽  
Free Form ◽  
Commercial Preparation ◽  
Apical Compartment ◽  
Proximal Tubular ◽  
Renal Proximal Tubule Cells

The capability of cyclosporin to produce direct injury to primary proximal tubular renal cells was studied. These cells, when grown on Millicell inserts, retain the functional polarity of the proximal tubule, i.e., generate a transepithelial pH gradient (apical compartment acidic) that is reversibly blocked by amiloride addition only if it is added to the apical compartment. Administration of ouabain to the basal compartment also blocks the generation of the transepithelial pH gradient. Additionally, the cells were more responsive to parathyroid hormone (PTH), a proximal tubule characteristic, than to arginine vasopressin (AVP), a distal tubule characteristic. The following substances were tested for their effect on the capacity of these cells to generate a pH gradient: Sandimmune, the commercial form of cyclosporin A; the free form of the drug; Cremophor EL, the vehicle used in the commercial preparation; and ethanol, the vehicle used to dissolve the free form. Sandimmune, at 25-50 microM, inhibited the generation of the pH gradient within 24 h. Surprisingly, Cremophor also blocked the development of a pH gradient, although somewhat less effectively. In contrast, 10 microM cyclosporin, regardless of the form tested, had no effect for up to 96 h. These findings show that cyclosporin, in the form of Sandimmune, has a direct toxic effect on these cells; they also suggest that the vehicle, Cremophor, may contribute to the well-established nephrotoxicity of cyclosporin A.

Studies of the urinary acidification defect induced by lithium

1982 ◽  
Vol 242 (1) ◽  
pp. F23-F29 ◽  
Author(s):  
N. Bank ◽  
P. D. Lief ◽  
H. S. Aynedjian ◽  
B. F. Mutz
Keyword(s):  
Proximal Tubule ◽  
Renal Tubular Acidosis ◽  
Electrical Potential ◽  
Distal Renal Tubular Acidosis ◽  
Distal Nephron ◽  
Luminal Membrane ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Convoluted Tubules

Experiments were carried out in rats and isolated turtle bladders to study the defect in H+ transport induced by LiCl. After 3-4 days of intraperitoneal LiCl, rats developed urinary findings of "distal" renal tubular acidosis. Proximal tubular fluid pH measured in situ by glass microelectrodes was higher in lithium-treated rats than in acidotic controls. Proximal fluid total CO2 [tCO2] was also higher, and the fraction of tCO2 leaving the proximal tubule was 14 vs. 7% (P less than 0.001). Impaired acidification was also apparent beyond distal convoluted tubules, as judged by normal distal tCO2 reabsorption but increased HCO3(-) in the urine. During NaHCO3 loading, the proximal defect was ameliorated but not the distal. Turtle bladder studies showed that mucosal lithium inhibits H+ secretion secondary to reducing transepithelial electrical potential, presumably by hyperpolarization of the luminal membrane. A similar mechanism may be responsible for lithium's effect on the distal nephron. Inhibition of proximal tubular HCO3(-) reabsorption is probably not attributable to electrical potential changes but might be due to interference of luminal membrane Na+ entry by Li+ and reduced (Na+ + Li+)-H+ exchange.

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