Renal Na,K-adenosine triphosphatase transport rate limits transcellular NaCl reabsorption in distal nephrons of volume-expanded dogs.
To examine whether the adenosine triphosphatase (Na,K-ATPase) transport rate regulates transcellular NaCl reabsorption, experiments were performed on anesthetized volume-expanded dogs. Ouabain was injected into the renal artery in doses inhibiting 10 to 80% of the renal Na,K-ATPase activity. Acetazolamide was administered before ouabain to render the NaHCO3 reabsorption and associated NaCl reabsorption constant during variations in the glomerular filtration rate. Ouabain reduced sodium reabsorption significantly after inhibiting 20% of the Na,K-ATPase. By inhibiting 80% of the Na,K-ATPase, NaCl reabsorption was reduced by 40 to 50% without affecting NaHCO3 reabsorption. During mechanical constriction of the suprarenal aorta, the remaining NaCl reabsorption was constant until the glomerular filtration rate was lowered by about 50%. Bound ouabain and the remaining Na,K-ATPase activity were distributed between the cortex and medulla in proportion to the Na,K-ATPase activity before ouabain injection. The reduction in NaCl reabsorption and ouabain binding were correlated (r = 0.90), the slope suggesting a turnover for ATP similar to the in vitro turnover of 5700 ATP min-1 estimated from the relationship between the remaining Na,K-ATPase activity and bound ouabain (r = 0.95). We conclude that transcellular reabsorption of NaCl in the distal nephron reaches a maximum in volume-expanded dogs by saturating the sodium sites of Na,K-ATPase because even a small dose of ouabain inhibits NaCl reabsorption and because the calculated turnover for Na,K-ATPase activity is similar to in vitro maximum estimates. The Na,K-ATPase transport rate, therefore, limits transcellular NaCl reabsorption in volume-expanded dogs.
D000042:Absorption; D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002712:Chlorides / Q000378:metabolism; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology; D009399:Nephrons / Q000201:enzymology* / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D002712:Chlorides; D012965:Sodium Chloride; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D000086:Acetazolamide