Evidence for PAH extraction from superficial cortical efferent vessel plasma

1983 ◽  
Vol 245 (5) ◽  
pp. F577-F583
Author(s):  
S. W. Weinstein ◽  
R. Klose ◽  
A. M. Kumar
Keyword(s):  
Proximal Tubule ◽  
Tubular Secretion ◽  
Proximal Convoluted Tubule ◽  
Peritubular Capillary ◽  
Blood Samples ◽  
Rapid Extraction ◽  
Peritubular Capillaries ◽  
Pars Recta ◽  
Proximal Tubular

Consistent with its anatomical association with the proximal tubule we have previously shown that superficial cortical efferent vessel blood contains an admixture of early and late proximal tubular reabsorbate. Since tubular secretion of p-aminohippurate (PAH) occurs predominantly in the late proximal tubule, extraction of this compound should occur preferentially from efferent vessel blood. As a result, the midportion of the proximal convoluted tubule supplied by the more downstream peritubular capillaries would receive blood containing a disproportionately reduced concentration of PAH. To study this, proximal and distal tubular fluid and efferent vessel blood samples were collected from rats. The data confirm that preferential secretion of PAH occurs in the pars recta and demonstrate that PAH is extracted from efferent vessel plasma by the pars recta. This in turn preferentially reduces PAH concentration in early postglomerular blood before it reaches the peritubular capillary network. We speculate that PAH and similar substances secreted by the pars recta are short-circuited by rapid extraction from early postglomerular blood, reducing their delivery to the mid-proximal convoluted tubule. Such circumstances must be considered in any analysis of organic compound secretion by the in vivo proximal tubule.

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.

Cortical interstitium as a site for solute polarization during tubular absorption

1988 ◽  
Vol 254 (6) ◽  
pp. F813-F823 ◽  
Author(s):  
J. C. Williams ◽  
J. A. Schafer
Keyword(s):  
Proximal Tubule ◽  
Capillary Permeability ◽  
Peritubular Capillary ◽  
Solute Permeability ◽  
True Value ◽  
Peritubular Capillaries ◽  
Tubular Lumen ◽  
The Difference ◽  
Solute Polarization

The possibility that significant concentration differences could exist between the interstitial fluid and capillary plasma was investigated by modeling the renal cortex as the following three compartments: tubular lumen, interstitium, and capillary lumen. A simple analysis of this system suggests that for the interstitium surrounding a proximal tubule, the concentration in the interstitium of a solute like glucose could be well over 1 mM greater than in the peritubular capillary if the solute permeability of the peritubular capillary were like that measured in other organs (i.e., less than 10 micron/s). The effect of varying capillary permeability on the interstitial concentrations of several solutes was examined using a modification of a model of the proximal tubule, and results were found to be similar to those obtained with the simpler analysis for glucose. This model was also used to see if placing an osmotic difference between the tubule lumen and capillary could cause significant solute polarization within the interstitium, as might occur in an experiment to measure the osmotic water permeability (Pf) of the proximal tubule in vivo. The results show that an apparent Pf calculated from the difference between the osmolalities of tubular perfusate and peritubular plasma is likely to underestimate the true Pf of the proximal tubule. Even for a high value of capillary permeability (10 micron/s, which allows relatively rapid diffusion between capillary and interstitium), the model predicts that the apparent Pf may underestimate the true value by half. Thus the analyses presented suggest that if the permeability of renal peritubular capillaries is similar to that measured in other organs the composition of the interstitium may be significantly different from capillary plasma, a situation that would have great impact on our view of the mechanism of volume absorption in the proximal tubule in vivo.

Direct action of aldosterone on bicarbonate reabsorption in in vivo cortical proximal tubule

2009 ◽  
Vol 296 (5) ◽  
pp. F1185-F1193 ◽  
Author(s):  
Patricia Silva Pergher ◽  
Deise Leite-Dellova ◽  
Margarida de Mello-Aires
Keyword(s):  
Proximal Tubule ◽  
Direct Action ◽  
Rat Kidney ◽  
Free Calcium ◽  
Mineralocorticoid Receptor Antagonist ◽  
Control Value ◽  
Bicarbonate Reabsorption ◽  
Peritubular Capillaries ◽  
Inhibitor Of Protein Synthesis

The direct action of aldosterone (10−12 M) on net bicarbonate reabsorption ( JHCO3−) was evaluated by stationary microperfusion of an in vivo middle proximal tubule (S2) of rat kidney, using H ion-sensitive microelectrodes. Aldosterone in luminally perfused tubules caused a significant increase in JHCO3− from a mean control value of 2.84 ± 0.08 [49/19 ( n° of measurements/ n° of tubules)] to 4.20 ± 0.15 nmol·cm−2·s−1 (58/10). Aldosterone perfused into peritubular capillaries also increased JHCO3−, compared with basal levels during intact capillary perfusion with blood. In addition, in isolated perfused tubules aldosterone causes a transient increase of cytosolic free calcium ([Ca2+]i), monitored fluorometrically. In the presence of ethanol (in similar concentration used to prepare the hormonal solution), spironolactone (10−6 M, a mineralocorticoid receptor antagonist), actinomycin D (10−6 M, an inhibitor of gene transcription), or cycloheximide (40 mM, an inhibitor of protein synthesis), the JHCO3− and the [Ca2+]i were not different from the control value; these drugs also did not prevent the stimulatory effect of aldosterone on JHCO3− and on [Ca2+]i. However, in the presence of RU 486 alone [10−6 M, a classic glucocorticoid receptor (GR) antagonist], a significant decrease on JHCO3− and on [Ca2+]i was observed; this antagonist also inhibited the stimulatory effect of aldosterone on JHCO3− and on [Ca2+]i. These studies indicate that luminal or peritubular aldosterone (10−12 M) has a direct nongenomic stimulatory effect on JHCO3− and on [Ca2+]i in proximal tubule and that probably GR participates in this process. The data also indicate that endogenous aldosterone stimulates JHCO3− in middle proximal tubule.

Response to parathyroid hormone in defined segments of proximal tubule

1976 ◽  
Vol 230 (2) ◽  
pp. 286-290 ◽  
Author(s):  
RJ Hamburger ◽  
NL Lawson ◽  
JH Schwartz
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Proximal Convoluted Tubule ◽  
Base Line ◽  
Fluid Absorption ◽  
Functional Heterogeneity ◽  
Intrinsic Absorption ◽  
Pars Recta ◽  
Intrinsic Capacity ◽  
Control Fluid

Previous investigations have suggested that there is a functional heterogeneity along the length of the proximal convoluted tubule. This study was designed to confirm and extend these suggestions by examining the intrinsic absorption of fluid and the effect of parathyroid hormone (PTH) on net fluid absorption in isolated, anatomically defined segments of rabbit superficial proximal tubules. The EPCT (early proximal convoluted tubule), LPCT (late proximal convoluted tubule), and PR (pars recta) segments were studied under controlled conditions by the isolated perfused tubule technique. In 23 EPCT, base-line fluid absorption was 1.38 +/- 0.04 (SE), a rate significantly higher than those of 11 LPCT (0.62 +/- 0.02; P less than 0.001) and 12 PR (0.52 +/- 0.03 nl mm-1 min-1, P less than 0.001) segments. In 10 EPCT, mean control fluid absorption was 1.31 +/- 0.04 nl mm-1 min-1; addition of PTH resulted in a decrease to 0.95 +/- 0.05 nl mm-1 min-1 (P less than 0.001); and, after removal of PTH, fluid absorption increased (P less than 0.001). Parathyroid hormone had no effect on either seven LPCT segments or six PR segments. These results demonstrate differences in intrinsic capacity to absorb fluid by anatomically defined segments of the rabbit proximal tubule. This functional heterogeneity is further supported by the observed differential response to PTH by the various anatomic segments of the proximal tubule.

Evidence for electroneutral sodium chloride transport in rat proximal convoluted tubule

1986 ◽  
Vol 250 (4) ◽  
pp. F644-F648
Author(s):  
K. J. Howlin ◽  
R. J. Alpern ◽  
C. A. Berry ◽  
F. C. Rector
Keyword(s):  
Sodium Chloride ◽  
Active Transport ◽  
Sodium Transport ◽  
Chloride Transport ◽  
Proximal Convoluted Tubule ◽  
Organic Solutes ◽  
Nacl Transport ◽  
Proximal Tubular ◽  
High Chloride

One- to two-thirds of NaCl absorption in the late proximal convoluted tubule (no luminal organic solutes present) is inhibited by cyanide and thus is dependent on active transport. To examine whether this active transport-dependent NaCl transport is electrogenic or electroneutral, the effect of cyanide on transepithelial potential difference (PD) was measured in the rat proximal convoluted tubule microperfused in vivo. In the presence of an ultrafiltrate-like luminal perfusate containing glucose and alanine, cyanide addition caused the transepithelial PD to change from -0.44 +/- 0.04 to -0.05 +/- 0.03 mV (P less than 0.001). In the presence of a late proximal tubular fluid (high chloride, low bicarbonate, no organics), the transepithelial PD was 1.23 +/- 0.06 mV and was unchanged at 1.19 +/- 0.05 mV after cyanide addition (NS). To eliminate the possibility that an effect of cyanide on a putative acidification-dependent lumen-positive PD was concealing an effect on an electrogenic sodium transport-dependent lumen-negative PD, the above studies were repeated in the presence of acetazolamide. Cyanide did not affect the transepithelial PD (1.17 +/- 0.05 vs. 1.07 +/- 0.06 mV, NS). We conclude that, although cyanide-inhibitable NaCl transport is electrogenic in the presence of luminal organic solutes, it does not generate a transepithelial PD in their absence and therefore is electroneutral.

scholarly journals Therapy with antisense TGF-β1 oligodeoxynucleotides reduces kidney weight and matrix mRNAs in diabetic mice

2000 ◽  
Vol 278 (4) ◽  
pp. F628-F634 ◽  
Author(s):  
Dong Cheol Han ◽  
Brenda B. Hoffman ◽  
Soon Won Hong ◽  
Jia Guo ◽  
Fuad N. Ziyadeh
Keyword(s):  
Proximal Tubule ◽  
High Glucose ◽  
Leucine Incorporation ◽  
Diabetic Mice ◽  
Renal Hypertrophy ◽  
Kidney Weight ◽  
Cell Hypertrophy ◽  
Proximal Tubular ◽  
Tgf Β1

Inhibition of gene expression by antisense oligodeoxynucleotides (ODNs) relies on their ability to bind complementary mRNA sequences and prevent translation. The proximal tubule is a suitable target for ODN therapy in vivo because circulating ODNs accumulate in the proximal tubule in high concentrations. Because increased proximal tubular transforming growth factor- β1 (TGF-β1) expression may mediate diabetic renal hypertrophy, we investigated the effects of antisense TGF-β1 ODN on the high-glucose-induced proximal tubular epithelial cell hypertrophy in tissue culture and on diabetic renal hypertrophy in vivo. Mouse proximal tubular cells grown in 25 mM d-glucose and exposed to sense ODN as control (1 μM) exhibited increased3[H]leucine incorporation by 120% and total TGF-β1 protein by 50% vs. culture in 5.5 mM d-glucose. Antisense ODN significantly decreased the high-glucose-stimulated TGF-β1 secretion and leucine incorporation. Continuous infusion for 10 days of ODN (100 μg/day) was achieved via osmotic minipumps in diabetic and nondiabetic mice. Sense ODN-treated streptozotocin-diabetic mice had 15.3% increase in kidney weight, 70% increase in α1(IV) collagen and 46% increase in fibronectin mRNA levels compared with nondiabetic mice. Treatment of diabetic mice with antisense ODN partially but significantly decreased kidney TGF-β1 protein levels and attenuated the increase in kidney weight and the α1(IV) collagen and fibronectin mRNAs. In conclusion, therapy with antisense TGF-β1 ODN decreases TGF-β1 production and attenuates high-glucose-induced proximal tubular cell hypertrophy in vitro and partially prevents the increase in kidney weight and extracellular matrix expression in diabetic mice.

scholarly journals Renoprotective Effects of Nobiletin on High Glucose-Induced Loss of Proximal Tubular Microvilli

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 412-412
Author(s):  
Min kyung Kang ◽  
Dongyeon Kim ◽  
Young-Hee Kang
Keyword(s):  
Proximal Tubule ◽  
High Glucose ◽  
Citrus Fruit ◽  
Cellular Polarity ◽  
Funding Sources ◽  
In Vivo Animal Model ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

Abstract Objectives Kidney proximal tubular epithelium has microvillar brush borders, which is critical to renal reabsorption. Hyperglycemia induce change the loss of brush border and cellular polarity, tight junction disruption. Nobiletin is a polymethoxyflavone present in citrus fruit and peels, and has anti-inflammatory effects. This study investigated the renoprotective effects of nobiletin on proximal tubule microvillar ultrastructure and reabsorption under diabetic condition. Methods Human renal proximal tubular epithelial cells (RPTEC) were incubated in a media exposed to 33 mM glucose in the absence and presence of 1–20 μM nobiletin up to 6 days. Antibodies F-actin, villin, cubulin, megalin, SGLT2 and GLUT2 were used for Western blot analysis. The in vivo animal model employed db/db mice orally administrated with 10 mg/kg of nobiletin. Extracts of tissues were subjected to Western blotting or immunohistochemical staining. Results High glucose declined expression of F-actin and villin required for the assembly of proximal tubule microvilli. In addition, the expression of glucose uptake proteins of GLUT2 and SGLT2 was prompted in hyperglycemia. However, nontoxic nobiletin enhanced the expression of F-actin reduced by high glucose, while the elevated expression of the GLUT2 and SGLT2 was attenuated by nobiletin. In the in vivo study, oral administration of 10 mg/kg nobiletin inhibited loss of tubular microvilli through restoring expression of F-actin and villin in diabetic kidneys. Furthermore, nobiletin reduced expressions of GLUT2 and the albumin uptake receptors of cubulin and megalin in db/db mouse kidneys. Conclusions These results demonstrated that nobiletin curtailed loss of the proximal tubular microvillar proteins responsible for tubular reabsorption. Nobiletin may be a potent renoprotective agent counteracting diabetes-associated proximal tubular dysfunctions leading to kidney failure. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (2017R1A6A3A04011473).

scholarly journals Microcirculation: nexus of comorbidities in diabetes

2007 ◽  
Vol 293 (2) ◽  
pp. F486-F493 ◽  
Author(s):  
Constance Temm ◽  
Jesus H. Dominguez
Keyword(s):  
Metabolic Syndrome ◽  
Large Scale ◽  
Interstitial Fibrosis ◽  
Peritubular Capillary ◽  
Tubular Atrophy ◽  
The Metabolic Syndrome ◽  
Peritubular Capillaries ◽  
Obese Rats ◽  
Capillary Dysfunction

Generalized capillary dysfunction is a morbid element in the metabolic syndrome, and it is likely involved in its complications. We tested the hypothesis that vast amounts of serum albumin previously observed in kidneys of rats with the metabolic syndrome were caused, in part, by leakage from renal peritubular capillaries. We report herein large scale leaks of plasma fluid in peritubular capillaries of rats with the metabolic syndrome. This finding was directly demonstrated in vivo, and the presence of leftover albumin residue confirmed the leak in postmortem kidney specimens. Moreover, renal interstitial fibrosis and tubular atrophy were found in a distribution similar to the leaked renal albumin in obese rats. We suggest that there is an important link between peritubular capillary damage and interstitial fibrosis, represented as tubulointerstitial disease in the metabolic syndrome. We propose that maintenance of the peritubular microcirculation may improve renal outcomes in diabetes and the metabolic syndrome.

Determinants of proximal tubular reabsorption as mechanisms of glomerulotubular balance

1978 ◽  
Vol 235 (2) ◽  
pp. F142-F150 ◽  
Author(s):  
B. J. Tucker ◽  
R. C. Blantz
Keyword(s):  
Proximal Tubule ◽  
Filtration Rate ◽  
Oncotic Pressure ◽  
Peritubular Capillary ◽  
Nephron Filtration Rate ◽  
Vein Occlusion ◽  
Proximal Tubular ◽  
Range Of Values ◽  
Proximal Tubular Reabsorption ◽  
Glomerulotubular Balance

The determinants of absolute proximal reabsorption (APR) were studied in four groups of rats during hydropenia, partial renal vein occlusion (RVO), saline expansion, and RVO after saline expansion. Nephron filtration rate (SNGFR), nephron plasma flow (RPF), APR, and proximal tubule (Pt) peritubular capillary (HPc), and interstitial (HPi) hydrostatic pressures were measured by micropuncture techniques. Subcapsular space (pii) and star peritubular capillary (piE) oncotic pressures were also determined. The peritubular capillary permeability coefficiency (LpAR) and the corresponding effective reabsorptive pressure (ERP) were computed, where APR = LpAR . ERP, and ERP = net reabsorptive pressure across the peritubular capillary. The results indicate that APR correlates best with SNGFR (P less than 0.05), but not with (pii - HPi), RPF, or LpAR. There was a significant relationship between piE and LpAR, where LpAR fell with increases in piE (P less than 0.01). In conclusion, 1) changes in absolute proximal reabsorption correlate best with changes in nephron filtration rate but not with (pii - HPi) across this range of values, 2) changes in efferent oncotic pressure (piiE) correlated inversely with LpAR, and 3) glomerulotubular balance in the proximal tubule can be partially attributed to intraluminal factors.

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.

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