Renal sodium-potassium-activated adenosine triphosphatase and sodium reabsorption

The 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 ranging from 0.4 to 0.9 mug/kg/min (low dose) and from 1.0 to 4.0 mug/kg/min (high dose). A significant natriuresis occurred with both dose ranges which was accompanied by inhibition of Na(+),K(+)-ATPase of cortex and medulla 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 (T(c) (H2O)). 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 kidney can rely on other sodium reabsorptive mechanisms depending on the rate of enzyme inhibition, so that natriuresis may not occur at all if depression in activity occurs "slowly." The nature of these mechanisms is not clear.