Energetics of tubular sodium reabsorption sensitive to ethacrynic acid and ouabain.
Ouabain reduces renal oxygen consumption more extensively than ethacrynic acid despite similar natriuretic effects. Therefore, ethacrynic acid, which does not inhibit Na-K-ATPase, might stimulate energy metabolism unrelated to net sodium reabsorption. Experiments were performed on anesthetized dogs that had received isotonic saline intravenously corresponding to 10% of body wt and acetazolamide (100 mg.kg-1 i.v.). Subsequent infusion of ouabain in nine dogs (120 nmol.kg-1 intrarenally) reduced sodium reabsorption and oxygen consumption in parallel, giving a delta Na/delta O2 ratio of 18.0 +/- 1.1. With ethacrynic acid (3 mg.kg-1 i.v.) in six other dogs the delta Na/delta O2 ratio averaged 24.5 +/- 1.4. In a third group of five dogs, ouabain administered after ethacrynic acid reduced sodium reabsorption and oxygen consumption to the same levels as when ouabain was given alone. Thus, the high oxygen consumption remaining after ethacrynic acid can be inhibited by ouabain. We propose that ethacrynic acid generates a futile cycling of sodium by Na-K-ATPase across the basolateral cell membrane that is not apparent as net sodium reabsorption and is stopped by ouabain.U
D000042:Absorption; D000818:Animals; D001693:Biological Transport, Active; D004285:Dogs; D004734:Energy Metabolism; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005260:Female; D007687:Kidney Tubules, Proximal / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D010101:Oxygen Consumption; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D004976:Ethacrynic Acid