Sugar interaction with the antiluminal surface of the proximal tubule in dog kidney

1977 ◽  
Vol 232 (5) ◽  
pp. F455-F460
Author(s):  
M. Silverman
Keyword(s):  
Proximal Tubule ◽  
Renal Vein ◽  
Sugar Transport ◽  
Inhibitory Effect ◽  
Transport Systems ◽  
High Dose ◽  
Multiple Indicator Dilution ◽  
Dog Kidney ◽  
Multiple Indicator

The pulse-injection multiple-indicator-dilution technique in vivo has been used to investigate bidirectional sugar interaction with the antiluminal surface of the nephron in dog kidney. Simultaneous renal vein and urine outflow curves were obtained for radiolabeled sugars known to interact with the antiluminal surface. The following sugars were tested relative to T-1824 albumin (plasma reference) and creatinine (extracellular reference) under conditions of high-dose phlorizin preloading (75–225 mg/kg): D-glucose, D-xylose, D-fucose, D-mannose, D-galactose, L-arabinose, myoinositol, and D-fructose. The results indicate that as the plasma concentration of phlorizin increases there is, first, a partial inhibition of sugar interaction at the antiluminal membrane so that only unidirectional uptake of sugar from blood to tubular cell is observed, followed by complete inhibition of sugar interaction at the peritubular face of the antiluminal membrane, resulting in superposition of sugar and creatinine curves in the renal vein effluent. Two possible interpretations exist. i) Phlorizin exerts its inhibitory action successively at the cytoplasmic and then at the peritubular face of the antiluminal membrane. Moreover, since all of the sugar substrates are inhibited by phlorizin, the data suggest that the sugar-membrane interaction takes place at a common site at the level of the proximal tubule. ii) Alternatively, the action of phlorizin could result from a metabolic inhibitory effect affecting multiple sugar transport systems at the antiluminal membrane.

In vivo indicator dilution kinetics of PAH transport in dog kidney

1989 ◽  
Vol 257 (1) ◽  
pp. F158-F158
Author(s):  
M. Silverman ◽  
C. Whiteside ◽  
C. J. Lumsden ◽  
H. Steinhart
Keyword(s):  
Renal Vein ◽  
Indicator Dilution ◽  
Dilution Technique ◽  
Physiological Conditions ◽  
Multiple Indicator Dilution ◽  
Dog Kidney ◽  
Multiple Indicator ◽  
Kinetics Of ◽  
Experimental Runs

Pages F255–F265: M. Silverman, C. Whiteside, C. J. Lumsden, and H. Steinhart. “In vivo indicator dilution kinetics of PAH transport in dog kidney.” Two important early studies of PAH transport in the kidney were carried out using the pulse-injection, multiple indicator dilution technique (MID). These references were overlooked in our citations. Page F261: the text should read “Probenecid is a known inhibitor of organic ion transport. Chinard et al. (35) noted that probenecid doses of 25 mg/kg body wt, when administered to dogs 20–30 min prior to an MID run, resulted in renal vein outflow curves for hippurate nearly identical to those of simultaneously injected creatinine. Figure 5 illustrates our control and experimental runs using probenecid as an inhibitor of [3H]PAH transport .” Page F263: the text should read “As Chinard showed in the earliest renal MID work on PAH known to us (36), the MID technique as used in this study has the advantage of allowing one to look at events occurring simultaneously at opposing nephron surfaces in the anesthetized dog, under nearly normal physiological conditions (see also Ref. 27).”

Mechanism of maleic acid-induced glucosuria in dog kidney

1976 ◽  
Vol 231 (4) ◽  
pp. 1024-1032 ◽  
Author(s):  
M Silverman ◽  
L Huang
Keyword(s):  
Brush Border ◽  
Maleic Acid ◽  
Brush Border Membrane ◽  
Multiple Indicator Dilution ◽  
Dog Kidney ◽  
Proximal Tubular ◽  
Multiple Indicator ◽  
Prior Administration

The multiple indicator-dilution technique in vivo and isolated brush-border membranes in vitro have been used to explore the mechanism of maleic acid-induced glucosuria in dog kidney. The interaction of D-glucose with the antiluminal membrane from the peritubular fluid surface is unaltered. It is demonstrated that alpha-methyl-D-glucoside (alpha MG) enters and exits from the proximal tubular cell only across the brush-border membrane. Then using alphaMG as a reference indicator, it is shown that maleic acid does not cause complete inhibition of D-glucose interaction with the antiluminal membrane from the cytoplasmic surface. The binding of [3H]phlorizin both in vivo and in vitro is not affected by prior administration of maleic acid, indicating that D-glucose interaction with the outside surface of the brush border is also not affected by maleic acid. The data are therefore consistent with the concept that maleic acid-induced glucosuria is due either to i) partial inhibition of D-glucose movement from cytoplasm across the antiluminal membrane into the blood, ii) stimulated movement back across the brush-border membrane into urine, or iii) a combination of the two effects.

Determination of glomerular permselectivity to neutral dextrans in the dog

1983 ◽  
Vol 245 (4) ◽  
pp. F485-F495
Author(s):  
C. Whiteside ◽  
M. Silverman
Keyword(s):  
Renal Vein ◽  
Renal Plasma Flow ◽  
Constant Infusion ◽  
Solute Flux ◽  
Left Renal Artery ◽  
Multiple Indicator Dilution ◽  
Transit Times ◽  
Multiple Indicator ◽  
T Values

The multiple-indicator-dilution (MID) technique was used to separate solute flux (Js) across the glomerular and postglomerular capillaries in vivo. Anesthetized mongrel dogs (n = 20) during mannitol diuresis received a pulse of extracellular indicators including 125I-albumin (plasma reference), [14C]inulin (glomerular reference), creatinine (interstitial reference), and a neutral [3H]dextran (specific mol wt between 10,000 and 24,000 dalton) in the left renal artery. Left renal venous and ureteric outflows were rapidly sampled. 3H-labeled dextrans 10,000-15,500 had renal vein mean transit times (t) greater than those of 125I-albumin, indicating postglomerular extraction. 3H-labeled dextrans greater than 15,500 had t values identical to those of 125I-albumin, indicating only unidirectional glomerular extraction. The glomerular fractional dextran extractions relative to simultaneously injected [14C]inulin (ED/Ei) were calculated from urine and renal vein outflow curves and ranged from 0.98 +/- 0.02 to 0.33 +/- 0.12 (SD) for mol wt 10,000 +/- 24,000. ED/Ei values were quantitatively identical to constant-infusion fractional clearances of the same dextrans. Renal plasma flow (RPF) was then deliberately reduced two-to threefold in the same dog. ED/Ei as measured by the MID technique remained unchanged during graded reduction in RPF. In constant-infusion experiments RPF was reduced from 5.78 to 2.77 ml X s-1 X 100 g-1 and GFR from 50.4 to 36.3 ml X min-1, but the fractional neutral dextran clearances remained constant. The predominance of convective solute flux across the dog glomerulus permitted calculation of glomerular reflection coefficients 0.03 +/- 0.06 to 0.85 +/- 0.03 (SD) for neutral 3H-labeled dextrans 10,000-24,000 dalton.

Trapping of urea by red cells in the kidney

1965 ◽  
Vol 209 (2) ◽  
pp. 253-263 ◽  
Author(s):  
Francis P. Chinard ◽  
Carl A. Goresky ◽  
Theodore Enns ◽  
Mary F. Nolan ◽  
R. Winifred House
Keyword(s):  
Carrier Transport ◽  
Red Cells ◽  
Equilibration Time ◽  
Similar System ◽  
Multiple Indicator Dilution ◽  
Transit Times ◽  
Dog Kidney ◽  
Multiple Indicator

Outflow patterns of T-1824, urea, thiourea, and creatinine have been determined in the dog kidney in vivo and in situ as a function of the arterial hematocrit by means of the multiple indicator-dilution technique. The mean transit times of T-1824, urea, and creatinine decrease and converge as the hematocrit decreases. The outflow patterns of urea are anomalous: a) there is precession of urea over creatinine and thiourea; b) the transit times of urea are shorter than those of creatinine and thiourea; c) the recoveries of urea are greater than those of creatinine at normal and high hematocrit values. Thiourea has a longer equilibration time with red cells than urea. Prior incubation of thiourea with red cells results in precession of thiourea over urea. These results are considered evidence of transient trapping of urea in red cells during their passage through the glomerular capillaries. The similarity of the urea outflow curves to curves of substances known to participate in a membrane carrier transport system by the tubule cells from the antiluminal side suggest that urea may participate in a similar system.

Transcapillary exchange of molecular weight markers in the postglomerular circulation: application of a barrier-limited model

1982 ◽  
Vol 242 (5) ◽  
pp. F436-F446
Author(s):  
C. Trainor ◽  
M. Silverman
Keyword(s):  
Molecular Weight ◽  
Excluded Volume ◽  
Excluded Volume Effects ◽  
Multiple Indicator Dilution ◽  
Filtration Barrier ◽  
Transit Times ◽  
Multiple Indicator ◽  
Dilution Experiments ◽  
Volume Effects

The permselectivity of the postglomerular capillary wall was studied by performing pulse-injection multiple indicator-dilution experiments on dog kidneys in vivo, using simultaneous injection of T1824-labeled albumin (plasma reference), creatinine (extracellular reference), and one or two radioactively labeled indicators: raffinose (595 dalton), vitamin B12 (1,357 dalton), or inulin (approximately 5,000 dalton). The urine transit patterns superimposed for all these except albumin, suggesting equal permeability for these molecular weight markers at the level of the glomerular filtration barrier. But the renal vein mean transit times progressively decreased. Therefore, their apparent interstitial volumes of distribution decrease with increasing molecular weight. This could be due to several factors acting singly or in combination: reduced capillary permeability in the postglomerular microcirculation; restricted diffusion in the postglomerular interstitium; or excluded volume effects. Evidence suggested that the effect was due to a combination of permeability and exclusion volume effects. To assess the validity of this assumption, the barrier-limited model was compared with the experimental data. The results were analyzed (both hydropenic and mannitol-diuretic dogs) and best fits calculated using two independent parameters, permeability and excluded volume. For permeability (X10(-4) cm/s, mean +/- SD) the range of values was always greater than or equal to 15 for creatinine and raffinose, and greater than or equal to 12 for B12. The permeability for inulin was 6.9 +/- 1.4. When interstitial volume excluded was expressed as percentage of the volume available to creatine, the excluded volume was negligible for raffinose and B12 but 12 +/- 5% for inulin. During mannitol diuresis the permeability for creatinine and raffinose remained high, but the values tended to decrease for B12. The permeability of inulin decreased to 2.9 +/- 0.09. Mannitol diuresis increased the excluded volume of inulin but did not alter the creatinine, raffinose, or B12 value.

Endothelial extraction of tracer water varies with extravascular water in dog lungs

1987 ◽  
Vol 252 (2) ◽  
pp. H340-H348 ◽  
Author(s):  
F. P. Chinard ◽  
W. O. Cua
Keyword(s):  
Volume Of Distribution ◽  
Indicator Dilution ◽  
Lung Water ◽  
Limited Distribution ◽  
Multiple Indicator Dilution ◽  
Multiple Indicator ◽  
The Time Domain ◽  
Area Product ◽  
Extravascular Volume

In multiple indicator-dilution experiments, transvascular passage of a permeating indicator is conventionally derived from the up-slope separation of the curve of the permeating indicator from that of a vascular reference and is expressed as the extraction (Ec). Extraction may be limited by the barrier (barrier-limited distribution). It may be limited by the volume of distribution accessible to it; in the time domain of an indicator-dilution experiment, the passage to and distribution in the extravascular volume are rapid relative to the velocity of blood in the exchange vessels. We examine here the relations of the extraction of tracer water as tritium oxide (THO) [Ec(THO)] and of the extraction of tracer sodium as 22Na [Ec(22Na)] to extravascular lung water, delta V wev, by adding isotonic fluid to the gas phase of the lungs. The net convective transvascular passage of water is negligible relative to the transendothelial molecular exchange. In 10 experiments in vivo and in 10 experiments in isolated perfused lungs, Ec(THO) increases as delta V wev increases. Ec(22Na) and the permeability-surface area product (PS) for 22Na do not change as delta V wev increases. We conclude that the extraction of THO is determined mainly by the volume accessible to it (flow- or volume-limited distribution) and that the extraction of 22Na is determined mainly by the resistance of the endothelium (barrier-limited distribution). A diffusion limitation in the added alveolar fluid rather than a barrier limitation at the endothelium may moderate Ec(THO).

Endothelial adenosine transporter characterization in perfused guinea pig hearts

2000 ◽  
Vol 279 (4) ◽  
pp. H1502-H1511 ◽  
Author(s):  
Lisa M. Schwartz ◽  
Thomas R. Bukowski ◽  
James D. Ploger ◽  
James B. Bassingthwaighte
Keyword(s):  
Guinea Pig ◽  
Surface Area ◽  
Cell Types ◽  
Maximal Velocity ◽  
Passive Transport ◽  
Multiple Indicator Dilution ◽  
Luminal Membrane ◽  
Permeability Surface ◽  
Multiple Indicator

Adenosine (Ado), a smooth muscle vasodilator and modulator of cardiac function, is taken up by many cell types via a saturable transporter, blockable by dipyridamole. To quantitate the influences of endothelial cells in governing the blood-tissue exchange of Ado and its concentration in the interstitial fluid, one must define the permeability-surface area products ( PS) for Ado via passive transport through interendothelial gaps [ PS g(Ado)] and across the endothelial cell luminal membrane ( PS ecl) in their normal in vivo setting. With the use of the multiple-indicator dilution (MID) technique in Krebs-Ringer perfused, isolated guinea pig hearts (preserving endothelial myocyte geometry) and by separating Ado metabolites by HPLC, we found permeability-surface area products for an extracellular solute, sucrose, via passive transport through interendothelial gaps [ PS g(Suc)] to be 1.9 ± 0.6 ml · g−1 · min−1( n = 16 MID curves in 4 hearts) and took PS g(Ado) to be 1.2 times PS g(Suc). MID curves were obtained with background nontracer Ado concentrations up to 800 μm, partially saturating the transporter and reducing its effective PS ecl for Ado. The estimated maximum value for PS ecl in the absence of background adenosine was 1.1 ± 0.1 ml · g−1 · min−1 [maximum rate of transporter conformational change to move the substrate from one side of the membrane to the other (maximal velocity; V max) times surface area of 125 ± 11 nmol · g−1 · min−1], and the Michaelis-Menten constant ( K m) was 114 ± 12 μM, where ± indicates 95% confidence limits. Physiologically, only high Ado release with hypoxia or ischemia will partially saturate the transporter.

Exchange of multiple indicators across renal-like epithelia: a modeling study of six physiological regimes

1986 ◽  
Vol 251 (6) ◽  
pp. F1073-F1089
Author(s):  
C. J. Lumsden ◽  
M. Silverman
Keyword(s):  
Epithelial Transport ◽  
Transport Processes ◽  
Indicator Dilution ◽  
Mathematical Form ◽  
Multiple Indicators ◽  
Multiple Indicator Dilution ◽  
Tracer Movement ◽  
Wide Range ◽  
Multiple Indicator

Multiple indicator dilution (MID) provides a means of quantifying the unidirectional steady-state fluxes of in vivo tracer movement within organs. In this report a MID model of tracer exchange across renal-like epithelia is developed in mathematical form. Six regimes of epithelial transport function are defined on the basis of the relative sizes of the tracer fluxes. Evidence for the existence of each regime has previously been obtained empirically. These are net secretion, net reabsorption, kinetic sink, antiluminal drive, antiluminal equilibration, and antiluminal trapping. By means of the mathematical model, the indicator dilution properties of the six regimes are compared. The principal similarities and differences among the regimes are documented and related to the physical basis of the transport processes. The findings suggest that over a wide range of physiologically meaningful flux magnitudes the functional regimes can be distinguished via existing empirical methods of MID. The model provides an improved basis for carrying out these distinctions in specific applications.

Pulmonary vascular extraction and distribution of antipyrine with alveolar flooding

1995 ◽  
Vol 269 (5) ◽  
pp. H1811-H1819
Author(s):  
W. O. Cua ◽  
V. Bower ◽  
C. Tice ◽  
F. P. Chinard
Keyword(s):  
Tritiated Water ◽  
Indicator Dilution ◽  
Limiting Factor ◽  
Multiple Indicator Dilution ◽  
Transit Times ◽  
Before And After ◽  
Multiple Indicator ◽  
Dilution Experiments ◽  
Orthogonal Distribution

Transport characteristics of antipyrine (AP), 22Na+, and tritiated water (THO) were assessed in dog lungs by multiple indicator-dilution experiments in vivo with anesthesia and in isolated perfused preparations before and after alveolar flooding. In controls, outflow patterns of AP and THO were nearly identical. In flooding, AP and THO patterns separated. THO upslopes decreased and mean (t) and modal (tmax) transit times increased as flooding increased; AP initial upslopes remained relatively unchanged but t increased, whereas tmax decreased. Patterns of 22Na+ were unchanged. The results indicate 22Na+ limitation at the endothelium, AP limitation only at the epithelium, and no THO limitation. A mathematical model is based on axial and orthogonal distribution of AP and THO. With alveolar flooding, diffusional distance may be a limiting factor in this distribution.

Kinetic analysis of rat renal tubular transport based on multiple-indicator dilution method

1986 ◽  
Vol 251 (1) ◽  
pp. F103-F114
Author(s):  
N. Itoh ◽  
Y. Sawada ◽  
Y. Sugiyama ◽  
T. Iga ◽  
M. Hanano
Keyword(s):  
Indicator Dilution ◽  
Transport Systems ◽  
Secretory Process ◽  
Renal Tubular Cell ◽  
Linear Type ◽  
Multiple Indicator Dilution ◽  
Tubular Transport ◽  
Multiple Indicator ◽  
Renal Tubular Transport ◽  
Renal Tubular

New methods, based on the multiple-indicator dilution (MID) technique, to study the kinetic relations between the renal tubular cell entry process and the secretory process of drugs are proposed. [3H]Cimetidine was used as a model drug. T-1824-labeled albumin (a vascular reference), [14C]creatinine (an extracellular reference), and [3H]cimetidine were rapidly injected into the renal artery of isolated perfused rat kidney, and normalized outflow-time patterns were secured from rapidly sampled renal venous perfusate. A distributed two-compartment model was fitted to the dilution data by nonlinear least-squares regression, and the influx, efflux, and sequestration rate constants were estimated. Both the influx and the sequestration process (based on the unbound cimetidine concentration) had two transport systems (i.e., Michaelis-Menten-type saturable transport and linear-type passive transport), whereas the efflux process was independent of the intracellular cimetidine concentration. At the low dose of cimetidine the influx clearance was larger than those of the efflux and sequestration, whereas at the high dose no remarkable difference was observed among these three clearances due to the large decrease in the influx clearance. Thus the MID technique is a sensitive new method to study the rate-limited process of renal tubular transport in rats.

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