Stop-flow analysis of tubular transport of uric acid in rabbits

1964 ◽  
Vol 207 (6) ◽  
pp. 1265-1272 ◽  
Author(s):  
E. C. Beechwood ◽  
W. O. Berndt ◽  
Gilbert H. Mudge
Keyword(s):  
Uric Acid ◽  
Flow Analysis ◽  
Distal Tubule ◽  
Free Flow ◽  
Transport Systems ◽  
Clearance Ratio ◽  
Renal Handling ◽  
Pronounced Increase ◽  
Secretory Transport ◽  
Stop Flow

Various physiological and pharmacological aspects of the renal handling of uric acid have been investigated. In the majority of rabbits the free-flow urate-to-inulin clearance ratio was found to be less than 1, although some animals (about 20%) demonstrated net secretion. Despite the predominance of net reabsorption under free-flow conditions, the usual stop-flow pattern showed only a proximal secretory peak. No distal tubular activity was evident under any of the experimental circumstances studied. The administration of chlorothiazide, lactic acid, creatinine, or pyrazinoic acid caused a pronounced increase in the proximal secretory peak. Probenecid produced a depression of the secretory peak resulting in a net reabsorptive dip. This reversal of proximal tubular activity is taken as evidence for the presence of both secretory and reabsorptive mechanisms. The following phenomena have been found to be involved in the renal handling of uric acid by the rabbit: 1) filtration of urate at the glomerulus; 2) proximal reabsorptive and secretory transport systems which are drug sensitive; and 3) relative impermeability of the distal tubule to urate.

Stop-flow analysis of creatinine excretion in the dog

1962 ◽  
Vol 203 (6) ◽  
pp. 980-984 ◽  
Author(s):  
Robert E. Swanson ◽  
Ali A. Hakim
Keyword(s):  
Creatinine Clearance ◽  
Competitive Inhibition ◽  
Flow Analysis ◽  
High Plasma ◽  
Free Flow ◽  
Inulin Clearance ◽  
Plasma Creatinine ◽  
Clearance Ratio ◽  
Creatinine Concentration ◽  
Stop Flow

Urinary excretion patterns of creatinine and inulin under stop-flow conditions in male mongrel dogs were compared. Evidence for a weak creatinine secretory mechanism at the proximal tubule level include the following: 1) Exogenous creatinine in the stop-flow samples appears prior to inulin when both are injected midway during a 10-min ureteral clamping period. 2) The ratio of creatinine/inulin U/P values (creatinine clearance ratio) shows a peak and a distribution coextensive with PAH/inulin clearance ratios. 3) Self-depression of the peak stop-flow creatinine clearance ratio was obtained at high plasma creatinine concentrations. 4) High plasma p-aminohippuric acid levels depressed the free-flow and peak stop-flow creatinine clearance ratios and, conversely, high plasma creatinine concentration depressed free-flow and peak stop-flow PAH clearance ratios (competitive inhibition). 5) Probenecid reduced free-flow and peak stop-flow creatinine clearance ratios (creatinine secretory mechanism blocked). The mean free-flow creatinine/inulin clearance ratios in 44 clearance periods was 1.2±0.1 (sd), compared to the peak stop-flow ratio of 1.8±0.4 (sd) (N = 20) at plasma creatinine concentrations less than 20 mg/100 ml.

Localization of urate transport in the nephron of mongrel and Dalmatian dog kidney

1959 ◽  
Vol 197 (3) ◽  
pp. 601-603 ◽  
Author(s):  
Richard H. Kessler ◽  
Klaus Hierholzer ◽  
Ruth S. Gurd
Keyword(s):  
Flow Analysis ◽  
Secretory Activity ◽  
Distal Segment ◽  
Free Flow ◽  
Proximal Segment ◽  
Urate Transport ◽  
Dog Kidney ◽  
Stop Flow ◽  
Urate Reabsorption ◽  
Dalmatian Dog

Localization of urate transport within the nephrons of mongrel and Dalmatian dogs was studied by stop-flow analysis. In mongrel dogs urate concentrations and clearance ratios were lowest in the segment in which PAH was secreted. Urate clearance ratios of 0.7 in free-flow samples were reduced to about 0.3 in stop-flow samples from the proximal segment. In the distal segment urate clearance ratios did not differ significantly from ratios obtained in free-flow. Probenecid, in doses sufficient to block PAH secretion, inhibited urate reabsorption thereby increasing urate clearance. In contrast to these findings with mongrel dogs, the Dalmatians exhibited weak but definite urate secretion within the proximal segment. The action of probenecid in this strain of dogs was to stop all proximal secretory activity for urate thereby reducing urate clearance. It was suggested that mongrel and Dalmatian dogs transport urate by systems that are identical except for direction of urate movement.

Characterization of the Renal Handling of Vasopressin in the Dog by Stop-Flow Analysis*

Endocrinology ◽  
1981 ◽  
Vol 109 (6) ◽  
pp. 2089-2094 ◽  
Author(s):  
TOKIHISA KIMURA ◽  
LEONARD SHARE
Keyword(s):  
Flow Analysis ◽  
Renal Handling ◽  
Stop Flow

Influence of inorganic electrolytes and ouabain on uric acid transport

1965 ◽  
Vol 208 (4) ◽  
pp. 642-648 ◽  
Author(s):  
W. O. Berndt ◽  
E. C. Beechwood
Keyword(s):  
Uric Acid ◽  
Organic Acids ◽  
Potassium Concentration ◽  
Flow Analysis ◽  
Rabbit Kidney ◽  
Kidney Cortex ◽  
Acid Transport ◽  
Acid Accumulation ◽  
Stop Flow ◽  
Urate Reabsorption

The importance of certain inorganic electrolytes in the transport of some organic acids by the kidney has been demonstrated. The present study was undertaken to evaluate further the transport characteristics for uric acid. Slices of rabbit kidney cortex were found to accumulate urate with a dependency on the medium potassium concentration. At 5 mm potassium the urate uptake was about 50% of maximum, with optimal accumulation above 10–40 mm potassium. Rubidium or cesium were found to substitute successfully for potassium; both substances permitted better uric acid accumulation than did potassium. Removal of sodium from the medium to concentrations as low as 65 mm did not influence urate uptake. At 15 mm sodium the urate accumulation was markedly depressed. Ouabain was found to depress urate uptake. The inhibition produced by this substance could be reversed by elevation of the medium potassium. Stop-flow analysis on the rabbit indicated that ouabain increased the proximal secretory peak for uric acid. On the basis of experiments where ouabain and probenecid were administered together, it was possible to attribute the action of ouabain to blockade of urate reabsorption.

Localization of the Site of Action of Mercurial Diuretics by Stop Flow Analysis

1958 ◽  
Vol 195 (3) ◽  
pp. 558-562 ◽  
Author(s):  
Arthur J. Vander ◽  
Richard L. Malvin ◽  
Walter S. Wilde ◽  
Lawrence P. Sullivan
Keyword(s):  
Proximal Tubule ◽  
Flow Analysis ◽  
Distal Tubule ◽  
Sodium Concentration ◽  
New Technique ◽  
Osmotic Diuresis ◽  
Site Of Action ◽  
Stop Flow ◽  
Ureteral Occlusion ◽  
Lower Urinary

Experiments utilizing the new technique of ‘stop flow’ analysis have been performed to localize the renal site of action of mercurial diuretics. Control ureteral occlusions were done on dogs after stabilization of mannitol osmotic diuresis. After release of occlusion and collection of samples, either thiomerin or meralluride (4–8 mg Hg/kg) was administered and a second occlusion performed forty minutes later. The mercurials caused at least a 50% reduction in the mass of water and sodium reabsorbed by the proximal tubule during the brief period of occlusion. These reductions were equivalent so that the sodium concentration of the proximal reabsorbate always remained plasma-like. The mercurials did not interfere with the ability of the distal tubule to lower urinary sodium concentration during the period of ureteral occlusion.

Stop-flow analysis of the influence of pCO2 on renal tubular transport of K and H

1964 ◽  
Vol 206 (6) ◽  
pp. 1355-1360 ◽  
Author(s):  
A. G. Ramsay
Keyword(s):  
Flow Analysis ◽  
Distal Tubule ◽  
Respiratory Alkalosis ◽  
Reciprocal Relationship ◽  
Tubular Transport ◽  
K Secretion ◽  
Renal Tubular Transport ◽  
Renal Tubular ◽  
A Site ◽  
Stop Flow

The stop-flow procedure was used to study the transport of H and K ions in the renal tubule during conditions of high and low pCO2. The increased rate of K excretion during respiratory alkalosis was due primarily to marked increase of K secretion at a distal site. The interrupted stop flow showed that K reabsorption was decreased at a site just proximal to the secretory area. This made a smaller contribution to the increased K excretion. The reciprocal relationship between tubular transport of K and H was demonstrable. CO2 tension appeared to influence HCO3 reabsorption and H secretion in both the distal and proximal tubule, whereas its effect on K transport was confined to the distal tubule. Hypercapnia never completely obliterated the distal secretory site. It is suggested that a pCO2-dependent H carrier is not shared with K. The increased K secretion of hypocapnia is more likely the result of increased K within the distal tubular cells.

Inhibition of urate excretion by pyrazinoate: a micropuncture study

1975 ◽  
Vol 229 (6) ◽  
pp. 1604-1608 ◽  
Author(s):  
F Roch-Ramel ◽  
IM Weiner
Keyword(s):  
Proximal Tubule ◽  
Renal Clearance ◽  
Left Kidney ◽  
Distal Tubule ◽  
Major Effect ◽  
The Other ◽  
Free Flow ◽  
Clearance Ratio ◽  
Cebus Albifrons ◽  
Micropuncture Study

Anesthetized monkeys (Cebus albifrons) undergoing moderate mannitol diuresis were treated with infusions containing lithium urate to elevate the urate concentration in plasma to 45-68 mug/ml and containing the uricosuric drug, 2-nitroprobenecid, to enhance the renal clearance or urate. The urate/inulin clearance ratio was 0.55 +/- 0.03. When pyrazinoate was added to the infusion the clearance ratio fell to 0.26 +/- 0.02. Analysis of free-flow micropuncture samples revealed a major effect of pyrazinoate in the proximal tubule, although an additional, smaller action in the distal tubule could not be definitely excluded. When droplets containing [14C]urate and [3H]inulin were streaked on the surface of the left kidney more urate than inulin appeared in the urine from that kidney (but not the other) within the first 3 min after application. This "excess" excretion of urate could be largely eliminated by pretreatment with pyrazinoate. The results suggest that pyrazinoate inhibits secretion of urate in the proximal tubule.

Renal handling of zinc: effect of cysteine infusion

1981 ◽  
Vol 241 (5) ◽  
pp. F487-F494 ◽  
Author(s):  
D. K. Abu-Hamdan ◽  
S. D. Migdal ◽  
R. Whitehouse ◽  
P. Rabbani ◽  
A. S. Prasad ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Distal Tubule ◽  
Calcium Excretion ◽  
Distal Nephron ◽  
Experimental Conditions ◽  
Renal Handling ◽  
Clearance Studies ◽  
Anesthetized Dogs ◽  
Significant Change ◽  
Stop Flow

Zinc clearance studies in anesthetized dogs were performed during hydropenia, mannitol infusion, and infusion of mannitol plus ZnSO4, ZnCL2, or cysteine. Mannitol expansion caused no significant change in Zn clearance. ZnSO4 infusion increased filtered Zn 13-fold without changing clearance. Zn excretion increased only sixfold, indicating increased net Zn reabsorption. Cysteine infusion increased urinary Zn excretion 86-fold, indicating net tubular Zn secretion, some of which derived from nonplasma sources. Stop-flow studies localized Zn reabsorption to the distal nephron during infusion of mannitol and mannitol plus ZnSO4 or ZnCl2. Net Zn secretion was shown to occur in the proximal tubule during cysteine infusion with reversal of the distal reabsorption pattern seen during ZnSO4 and ZnCl2 infusion. Despite increased urinary Zn excretion during ZnSO4 infusion, calcium excretion was unaltered. During cysteine infusion dissociation of tubular handling of CA2+ and Zn occurred in both the proximal and distal tubule. These experiments demonstrate that the nephron under these experimental conditions is capable of both proximal secretion and distal reabsorption of Zn.

Renal handling of lead in dogs: stop-flow analysis

1979 ◽  
Vol 237 (5) ◽  
pp. F408-F414
Author(s):  
W. Victery ◽  
A. J. Vander ◽  
D. R. Mouw
Keyword(s):  
Flow Analysis ◽  
Renal Handling ◽  
Stop Flow
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