Distal Sodium Reabsorption Research Articles

Inhibition of distal tubular sodium reabsorption by angiotensin. II.

Angiotensin II or norepinephrine was infused directly into the left renal artery of anesthetized dogs undergoing mannitol diuresis, and the right and left kidneys were compared for GFR (Ccr or Cin), RPF (Cpah), sodium excretion, and distal stop-flow sodium and inulin patterns. Both angiotensin and norepinephrine caused similar reductions of GFR and RPF on the left, as compared with the right, but only angiotensin prevented normal lowering of left distal stop-flow sodium concentration, even when length of occlusion was 14 min. The minimum effective dose was 6–12 mµg/kg min, and maximal differences between left and right sodium minima occurred with 50 mµg/kg min. Distal inulin patterns were not altered by angiotensin, nor were "postocclusive" inulin patterns. Clearance data demonstrated that when GFR changes were taken into account angiotensin caused a relative increase in sodium excretion compared to control or norepinephrine-infused dogs. These stop-flow and clearance data support the hypothesis that angiotensin inhibits distal sodium reabsorption by a direct tubular effect. No attempt was made to evaluate possible effects of angiotensin on proximal tubular sodium reabsorption.

An investigation of the actions of aldosterone on perfused cat kidneys, by ureteric stop-flow analysis.

Stop-flow analysis, adapted for use on perfused cat kidneys, has been used for the study of the modifications induced in the reabsorption of salt, and water by blood from headless donor animals and by aldosterone.1. the supranormal rates of excretion of salt and water found when cat kidneys are perfused with blood from headless or bypophysectornized donor animals result from impairment of proximal water-linked salt reabsorption. Distal sodium reabsorption proceeds normally (cf. figs. 2 and 3).2. Aldosterone, in blood from headless animals, depresses further this impaired proximal reabsorption of salt and water arid so produces an overall diuretic and sodium-losing effect (fig. 4).3. Aldosterone, in blood from intact animals, increases not only the distal rate of sodium reabsorption but also the proximal water-linked reabsorption of salt and water (fig. 4). This explains the antidiuretic effect of aldosterone on these preparations.4. Oxytocin enhances the effects of aldosterone in blood from intact donor animals (cf. figs. 6 and 4). Oxytocin converts the diuretic action of aldosterone in blood from head-less animals (fig. 4) into an antidiuretic sodium retaining nne, by sensitizatioct of the proximal segments to the salt and water retaining action of aldosterone (cf. figs 5, 6 and 7).

Cadmium enhancement of proximal tubular sodium reabsorption.

Stop-flow studies were performed to localize the site of cadmium action on renal sodium reabsorption. In the untreated dog undergoing mannitol diuresis, a maximal lumen:plasma sodium gradient was established across the proximal tubule during free flow with no further lowering of luminal concentration during ureteral occlusion, Naprox/NaFF = 1.02 ± .05. During occlusions after cadmium, sodium concentrations in proximally trapped fluid were reduced below free-flow values, Naprox/NaFF = 0.85 ± .08. This difference between treated and untreated animals was statistically significant ( P = < .001) and indicates that cadmium enhances proximal sodium reabsorption. Although distal sodium patterns were unaltered by cadmium, it was not possible to rule out a possible distal site since distal sodium reabsorption is already virtually complete during occlusion in the untreated animal. Cadmium, given intravenously as Cd115, was not excreted in the urine.

Stop flow analysis of renal function in the monkey.

Stop flow analysis has been used to study renal function in the macaque monkey. Mannitol diuresis produced excretion of 58–70% of filtered water and 22–34% of filtered sodium. An absence of water and sodium reabsorption from the proximal tubule during ureteral occlusion was observed in three of four experiments, suggesting that this portion of the monkey nephron cannot transport sodium as efficiently as the canine proximal tubule during osmotic diuresis or that it is less permeable to water. Creatinine secretion was observed and localized to the same portion of the proximal tubule which secretes PAH. Inorganic phosphate and glucose reabsorption also occurred in the proximal tubule. Sodium, chloride, and potassium stop flow patterns were identical to those reported for the dog. Chlorothiazide caused an inhibition of distal tubular sodium reabsorption and an enhancement of potassium secretion in the distal nephron. Proximal tubular activity of the drug could not be evaluated.

Renal transport sites for K, H and NH3. Effect of impermeant anions on their transport

The stop flow technique was used to locate the sites of the renal transport mechanisms for potassium, hydrogen and ammonium. Data were obtained which indicate that these cations are secreted in a very distal area of the nephron, presumably in the collecting ducts. Potassium reabsorption also occurs in a distal area immediately proximal to the secretory site. Infusions of thiosulfate, ferrocyanide and phosphate alter the stop flow concentration patterns so that secretion of the cations appears to take place throughout the distal tubule and to be coextensive with distal sodium reabsorption. No clear indication of potassium reabsorption is evident under these circumstances. It is suggested that these anions, because of the impermeability of the distal tubule to them and because of their negative charge, attract hydrogen and potassium into the tubular lumen as sodium is reabsorbed. In effect, an abnormal exchange mechanism is created at a site proximal to that where active secretion of hydrogen and potassium occurs.

Localization of renal calcium transport; effect of calcium loads and of gluconate anion on water, sodium and potassium.

We have performed a first series of experiments using our stop flow technique to localize renal transport of calcium in dogs. Calcium is found to be actively reabsorbed in a far distal area but does not appear to be actively lowered in concentration in proximally derived samples. In a second series of dogs, elevation of plasma calcium by infusion of the salt CaCl2 caused a 43% reduction in the additional volume of water reabsorbed by the proximal tubule during stop flow. Calcium does not interfere with the active reabsorption of sodium in the distal area and does not cause significant increases in sodium excretion. In contrast calcium causes a considerable increase in potassium secretion at a far distal site. When calcium gluconate was employed, severe impairment of distal sodium and calcium reabsorption occurred in addition to the increased potassium secretion. We suggest that the gluconate anion restricts the movement of sodium, calcium and potassium electrostatically thus obligating cations to remain in the tubular urine depending upon their reabsorption potential.

Effects of adrenalectomy and aldosterone on proximal and distal tubular sodium reabsorption.

SummaryThe technic of stop-flow analysis has been used to localize the site of renal sodium reabsorption which is affected by adrenalectomy and aldosterone. Following adrenalectomy, the distal tubule was not able to reduce sodium concentration to the low value achieved during stop-flow in normal dogs. Following aldosterone administration this distal reabsorptive capacity was restored. No conclusion could as yet be made regarding the effects of aldosterone on the proximal tubule.