Multiple pumps for sodium reabsorption by the perfused kidney (original) (raw)

Renal Sodium-Potassium-Activated Adenosine Triphosphatase and Sodium Reabsorption

Journal of Clinical Investigation, 1972

role of renal Na+,K+-ATPase in sodium reabsorption was further examined in dogs in which digoxin, a specific inhibitor of the enzyme system, was infused into one renal artery in doses ranginig from 0.4 to 0.9 /Ag/kg/min (low dose) and from 1.0 to 4.0 Ag/kg/ min (high dose). A significant natriuresis occurred with both dose ranges which was accompanied by inhibition of Na+,K+-ATPase of cortex and nmedulla in the infused kidney. Despite over 90% enzyme inhibition in many experiments, at least 80% of the filtered sodium continued to be reabsorbed. The per cent change in enzyme activity correlated with the rate of digoxin administration and the total dose administered but not with changes in sodium excretion. Changes in medullary Na+,K+-ATPase activity, however, bore a direct relationship to alterations in fractional solute free water reabsorption (TcH1o). Inhibition of cortical enzyme activity alone was not associated with natriuresis, suggesting that medullary enzyme activity must be depressed for increased sodium excretion to occur during digoxin infusion. In high-dose experiments, significant inhibition of cortical and medullary enzyme in the contralateral control kidney was also observed, but natriuresis did not occur. In these experiments the rate at which digoxin reached the control kidney rose progressively but never equaled the rates in the directly infused kidney with either dose. Nevertheless, it is clear that under certain circumstances enzyme inhibition of either cortex or medulla need not be accompanied by natriuresis. We conclude that the major role of renal Na+,K+-ATPase is in sodium reabsorption in the medulla (ascending limb of Henle's loop) and that it has a relatively small role in proximal sodium reabsorption. The Dr. Tsaparas is a Hoechst International Fellow in Nephrology.

Energetics of sodium transport in the kidney

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1983

31P-NMR has been used to quantify inorganic phosphate (Pi) and high-energy phosphates in the isolated, functioning perfused rat kidney, while monitoring oxygen consumption, glomerular filtration rate and sodium reabsorption. Compared with enzymatic analysis, 100% of ATP, but only 25% of ADP and 27% of Pi are visible to NMR. This is indicative that a large proportion of both ADP and Pi are bound in the intact kidney. NMR is measuring free, and therefore probably cytosolic concentrations of these metabolites. ATP synthesis rate, measured by saturation transfer NMR shows the P:O ratio of 2.45 for the intact kidney. This is close to the theoretical value, suggesting the NMR visible pool is that which is involved in oxidative phosphorylation. The energy cost of Na transport, calculated from the theoretical Na: ATP of 3.0 exceeded the measured rate of ATP synthesis. Instead, Na:ATP for active transport in the perfused kidney was 12. Since the phospborylation potential (IATPI/IADPI× IPil) by NMR was 10000 M-1, the free-energy of ATP hydrolysis was 52 kJ/tool. Using this figure, the rate of ATP hydrolysis observed could fully account for the observed rate of sodium reabsorption.

Dependency of renal potassium excretion on Na, K-ATPase transport rate

Acta Physiologica Scandinavica, 1985

Potassium secretion may depend on the transport rate of Na, K-ATPase in basolateral cell membranes of distal tubular cells. To examine this hypothesis experiments were performed in anaesthetized dogs during inhibition of proximal potassium reabsorption by acetazolamide or mannitol (fractional potassium excretion 1.2 - 1.4) or additional stimulation of potassium secretion by ethacrynic acid (fractional potassium excretion 2.1). Ouabain in a dose which inhibits 70-80% of the Na, K-ATPase activity reduced fractional potassium excretion to 0.8 - 0.9 by an effect on distal tubular secretion since potassium transport in the proximal tubules was not affected. Ouabain-sensitive potassium excretion varied in proportion to ouabain-sensitive sodium reabsorption during variation in glomerular filtration rate, even at urinary sodium concentrations exceeding 80 mmol X 1(-1). In experiments without ouabain, saline infusion raised potassium excretion and sodium reabsorption until maximal Na,K-ATPase transport rate was reached, as judged from heat production measurements, but not during further increments in urine flow. After inhibition of Na,K-ATPase activity by hypokalaemia, potassium excretion and cortical heat production remained constant over a wide range of urine flow and sodium excretion. We conclude that potassium secretion is dependent on intact Na,K-ATPase activity and is stimulated by sodium delivery to the distal nephron until maximal transport rate of the enzyme is reached.

Solute transport and oxygen consumption along the nephrons: effects of Na+transport inhibitors

American Journal of Physiology-Renal Physiology, 2016

Sodium and its associated anions are the major determinant of extracellular fluid volume, and the reabsorption of Na+by the kidney plays a crucial role in long-term blood pressure control. The goal of this study was to investigate the extent to which inhibitors of transepithelial Na+transport (TNa) along the nephron alter urinary solute excretion and TNaefficiency and how those effects may vary along different nephron segments. To accomplish that goal, we used the multinephron model developed in the companion study (28). That model represents detailed transcellular and paracellular transport processes along the nephrons of a rat kidney. We simulated the inhibition of the Na+/H+exchanger (NHE3), the bumetanide-sensitive Na+-K+-2Cl−transporter (NKCC2), the Na+-Cl−cotransporter (NCC), and the amiloride-sensitive Na+channel (ENaC). Under baseline conditions, NHE3, NKCC2, NCC, and ENaC reabsorb 36, 22, 4, and 7%, respectively, of filtered Na+. The model predicted that inhibition of NHE3 ...