Micropuncture study of the effect of various diuretics on sodium reabsorption by the proximal tubules of the dog (original) (raw)
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Evidence for enhanced distal tubule sodium reabsorption in chronic salt-depleted dogs
Journal of Clinical Investigation, 1976
order to assess the renal tubular site(s) at which sodium reabsorption is enhanced in chronic sodium-depletion, seven normal dogs, six saltdepleted dogs, and three normal dogs receiving aldosterone were studied during a steady-state water diuresis under Pentothal anesthesia and during progressive hypotonic saline diuresis. For both maintenance of the water diuresis and progressive hypotonic saline diuresis 0.45% NaCl was used. During the steady state water diuresis delivery of sodium to the diluting segment of the nephron as approximated by solute-free water clearance + sodium clearance/glomerular filtration rate (CH2O + CN./GFR) was significantly lower in salt-depleted dogs compared to normal dogs with or without aldosterone. During progressive hypotonic saline infusion fractional free water excretion (CH20/GFR) was similar in all three groups as CHn>O + CNa/GFR increased up to 12-14 ml /min. 100 ml GFR. Thereafter, CH20/ GFR continued to rise in virtually a straight line in salt-depleted dogs but leveled off in normal dogs with or without aldosterone. These data demonstrate that enhanced sodium reabsorption in the diluting segment of the nephron is an important determinant of the renal sodium retention in chronic extracellular volume contraction in dogs in addition to confirming the presence of increased proximal tubule sodium reabsorption in these animals.
Chronic Effects of Chlorothiazide on Reabsorption by the Proximal Tubule of the Rat
Clinical Science, 1975
1. The renal response to a low-sodium diet alone and a low-sodium diet plus the daily oral administration of chlorothiazide was examined in rats. Sodium restriction resulted in a decrease in sodium excretion until day 4, after which it remained constant. The administration of chlorothiazide resulted in an initial natriuresis. By day 6, however, the natriuresis had abated and thereafter sodium excretion remained the same as that of the low-sodium group. 2. After the animals were in balance on their respective regimens, clearance and micropuncture studies were performed. The glomerular filtration rate was lower in the chlorothiazide-treated rats than in control rats and/or in the low-sodium group. End proximal tubule TF/Pinulin ratios were higher in the diuretic-treated animals than in control rats. TF/Pinulin ratios in low-sodium animals were lower than in the diuretic-treated animals but higher than in control rats. 3. These studies demonstrate that the escape from the chronic effec...
1992
Calcium transport through the luminal membrane of the distal tubule. I. Interrelationship with sodium. Calcium (Ca2) transport by isolated luminal membranes from rabbit renal distal tubule has been characterized. Ca2 uptake by these membrane vesicles exhibited saturation kinetics. In the absence of sodium (Nat) in the incubation medium, a low affinity system was observed with a KmCa2 of 2.83 0.64 m and Vmax of 3.03 0.48 pmol/g/l0 sec. A second type of kinetics was also detected with a high affinity and a low velocity (KmCa2 0.04 0.01 mM, 1.18 022 pmol/gf10 sec). The luminal membranes from proximal tubules showed a single system with a KmCa2 of 0.49 0.20 m and Vmax of 1.26 0.17 pmol/gIl0 sec. The presence of Na sharply decreased Ca2 uptake by the high affinity system of the membranes from distal tubules, increasing the KmCa2 to 0.07 mM 0.01 (P < 0.01) and decreasing the max to 0.27 pmol/g/10 sec (P < 0.005). This effect of Na was concentration-dependent, with a halfmaximal effect at 38 msi Na and a Hill coefficient of 0.9. In contrast, Na had no effect on Ca2 transport through the luminal membranes of proximal tubules nor on the low affinity system of the distal tubule. The composition of the intravesicular medium also influenced Ca2 uptake by the membranes from distal tubules. Compared to mannitol, trans-Na or K significantly reduced Ca2 transport. Finally, cis-K induced an increase in this transport. As found with Na, the effect of K was concentration-dependent, with a Hill coefficient of 0.42. It is concluded that: 1) the luminal membrane of the distal tubule fundamentally differs from the brush border membrane of the proximal tubule; 2) Na has an inhibitory effect on Ca2 uptake when applied on either side of the distal tubule membrane, and therefore probably binds at two different sites of the carriers in the membrane; 3) trans-K inhibits whereas cis-K enhances Ca2 transport in this membrane; and 4) the actions of Na and K are not dependent upon any exchange mechanism.
Atrial natriuretic peptide has no direct effect on proximal tubule sodium and water reabsorption
Pflügers Archiv, 1989
Infusion of ANP has been shown to increase the urinary excretion of sodium and water. However it is still controversial in which tubular segment sodium reabsorption is inhibited. To clarify this problem we have performed in vivo and in vitro studies to examine the direct effect of ANP on rat proximal tubules. The in vivo effect of ANP has been tested by using the micropuncture technique and in particular the shrinking droplet method that allows each investigated tubule to serve as its own control. Addition of either low (10-9 M) or high (2 x 10-6 M) concentrations of ANP to the luminal perfusate resulted in no significant change in isotonic fluid reabsorption (Jv). The same holds when the proximal tubules were perfused on both the tubular and peritubular side, with modified Ringer solution containing 10-9 M ANP. To examine possible in vitro effects of ANP we prepared highly purified proximal tubule suspension derived from rat renal cortex and monitored oxygen consumption (QO2) that is tightly coupled to sodium transport in this segment. Synthetic ANP, either at low (10 .9 M) or at high (10 .6 M) concentrations, did not affect basal rate of tubular respiration. Moreover the peptide hormone (10 .9 M) did not inhibit nystatin stimulated and ouabain sensitive QOz. These results indicate that the enhancement of renal sodium excretion induced by ANP is not related to a direct inhibition of sodium transport in the proximal tubule.
Reversible effects of acute hypertension on proximal tubule sodium transporters
American Journal of Physiology-Cell Physiology, 1998
Acute hypertension provokes a rapid decrease in proximal tubule sodium reabsorption with a decrease in basolateral membrane sodium-potassium-ATPase activity and an increase in the density of membranes containing apical membrane sodium/hydrogen exchangers (NHE3) [Y. Zhang, A. K. Mircheff, C. B. Hensley, C. E. Magyar, D. G. Warnock, R. Chambrey, K.-P. Yip, D. J. Marsh, N.-H. Holstein-Rathlou, and A. A. McDonough. Am. J. Physiol.270 ( Renal Fluid Electrolyte Physiol.39): F1004–F1014, 1996]. To determine the reversibility and specificity of these responses, rats were subjected to 1) elevation of blood pressure (BP) of 50 mmHg for 5 min, 2) restoration of normotension after the first protocol, or 3) sham operation. Systolic hypertension increased urine output and endogenous lithium clearance three- to fivefold within 5 min, but these returned to basal levels only 15 min after BP was restored. Renal cortex lysate was fractionated on sorbitol gradients. Basolateral membrane sodium-potassiu...
Multiple pumps for sodium reabsorption by the perfused kidney
Kidney International, 1976
Multiple pumps for sodium reabsorption by the perfused kidney. Several distinct transport mechanisms responsible for sodium reabsorption by the rat kidney can be identified by studying the function of isolated perfused kidneys. Approximately one-half of the fractional sodium reabsorption by the isolated perfused rat kidney appears to depend on Na-K-adenosine triphosphatase (AT-Pase) and is inhibited by ouabain. About 15 to 20% is associated with the reabsorption of bicarbonate and is blocked by acetazolamide. This fraction of transported sodium is unaffected by ouabain and therefore does not involve Na-K-ATPase. Neither furosemide nor ethacrynic acid produce further inhibition of sodium reabsorption in a kidney already exposed to ouabain and acetazolamide. Most of the residual transport of sodium is inhibited by cooling the perfused kidney, suggesting that it is powered by metabolic rather than physical sources of energy. Multiplicité des pompes qui assurent Ia reabsorption du sodium par le rein perfuse. Plusieurs mécanismes de transport distincts responsables de Ia reabsorption de sodium par le rein de rat peuvent être identifies par l'étude du fonctionnement de reins isolés perfusés. La moitié, approximativement, de Ia reabsorption fractionnelle du sodium par les reins isolés perfusés semble dCpendre de Ia Na-K-ATPase et est inhibée par l'ouabaTne. Environ 15 a 20% sont associés a Ia reabsorption du bicarbonate et bloquCs par l'acetazolamide. Cette fraction du sodium transporté n'est pas affectée par l'ouabaIne et donc n'implique pas Ia Na-K-ATPase. Ni le furosémide ni l'acide éthacrynique ne produisent d'inhibition supplementaire de Ia reabsorption de sodium par un rein déjà exposé a l'ouabaYne et a l'acetazolamide. La plus grande partie du transport résiduel du sodium est inhibée par le refroidissement du rein perfuse, ce qui suggère une source d'énergie métabolique plutôt que physique. The reabsorption of salt and water from the gbmerular filtrate is thought to be accomplished by one or more ion pumps located within renal tubular cells. The transport mechanism that has been best characterized is that dependent upon sodium-potassiumactivated adenosine triphosphatase (Na-K-ATPase). Studies of renal function in intact anesthetized dogs [I], in rats subjected to micropuncture [2] and in the isolated perfused rat kidney [3] suggest that approximately one-half of all the sodium reabsorbed by the kidney in these species is transported by a process
Journal of Clinical Investigation, 1988
To examine the renal tubular sites and mechanisms involved in the effects of hypooncotic volume expansion (VE) on renal electrolyte excretion, we performed clearance and isolated tubular perfusion studies using intact and thyroparathyroidectomized (TPTX) rabbits. We also examined the effect of VE on luminal brush border transport. In the microperfusion studies, proximal convoluted (PCT) and straight (PST) tubules were taken from rabbits without prior VE or after 30 min of 6% (body wt) VE. Acute VE increased the percentage excretion of Na, Ca, and P in TPTX animals and the percentage and absolute excretions of these ions in intact rabbits. In PST from VE animals, fluid flux (Jv) was depressed compared with Jv in PST from nonVE rabbits: Jv = 0.18i0.03, (VE) vs. 0.31±0.03 nl/mm. min, (non VE) P < 0.02. Phosphate transport (Jp) in the PST from VE animals was also depressed: Jp = 1.58±0.10 (VE) vs. 2.62±0.47 pmol/mm. min, (nonVE) P < 0.05. Similar results were obtained with TPTX animals. In the PCT from VE animals, Jv was decreased (0.49±0.10 (VE) vs. 0.97±0.14 nl/mm * min, (non VE) P < 0.02), but Jp was not affected significantly. Transport inhibition was stable over-90 min of perfusion. In the brush border vesicle studies, sodium-dependent phosphate transport was inhibited compared with that in control animals, at the 9-, 30-, and 60-s time points. These findings indicate that the inhibition of renal ionic transport by VE occurs in both PCT and PST and is, in part, the result of a direct effect of VE on tubular transport mechanisms.