Functional differences of ouabain and ethacrynic acid on renal potassium metabolism in dogs.
Current concepts provide inadequate explanations for the effects of ethacrynic acid (ECA) and ouabain (OUA) on renal potassium metabolism because neither the site of action, nor the tubular effects have been agrreed upon. In the present study on anaesthetized dogs, in vivo inhibitory effects of ECA on mitochondria or Na-K-ATPase were excluded. Firstly, ECA hardly reduced outer medullary metabolic rates in kidneys exposed to OUA  and 2,4-dinitrophenol. Secondly, whereas OUA reduced renal Na-KATPase activity by 78% and induced parenchymal potassium release into the renal vein, none of these effects were observed during injection of ECA. During free flow, sodium reabsorption was equally reduced by the two drugs, but fractional potassium excretion was 0.54 +/-0.04 after OUA and 0.99 +/-0.02 after ECA. OUA alone or combined with ECA inhibited almost all ion transport in the distal 60% of the tubular volume as revealed by stop-flow. During ECA alone, chloride reabsorption was reduced more than sodium reabsorption because sodium was exchanged for potassium. ECA and SO4(2-) infusion produced similar stop-flow patterns. Thus, OUA is bound to Na-K-ATPases functionally located to the peritubular cell membrane. ECA promotes potassium secretion probably by inhibiting cellular anion entry at the luminal membrane.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002740:Chlorothiazide / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005260:Female; D006358:Hot Temperature; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000652:urine; D012965:Sodium Chloride / Q000494:pharmacology; D013431:Sulfates / Q000494:pharmacology
D004140:Dinitrophenols; D013431:Sulfates; D012965:Sodium Chloride; D010042:Ouabain; D002740:Chlorothiazide; D012964:Sodium; D000251:Adenosine Triphosphatases; D004976:Ethacrynic Acid; D011188:Potassium