MAXIMAL EFFECTS OF OUABAIN ON RENAL SODIUM REABSORPTION AND OUABAIN-SENSITIVE ADENOSINE TRIPHOSPHATASE ACTIVITY IN THE DOG

¹ Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas

The cardiac toxicity of ouabain has previously prevented the definitive establishment of the maximal effects of the drug on renal Na⁺ reabsorption and ouabain-sensitive adenosine triphosphatase. In this study we increased the dose of ouabain to 120 to 138 µg/kg by cross-transfusing two dogs to enlarge the volume of distribution of the glycoside infused into the left renal artery of one dog in the pair. Each dog received Ringer's solution at a rate of 10 ml/min i.v. After Na⁺ reabsorption was determined the kidneys were removed and the enzyme activity was measured in whole organ homogenates. In the ouabain-treated kidney, the reduction of Na⁺ reabsorption averaged 26% of the filtered load with 89% of the enzyme activity inhibited. These results were similar to those after 70 to 80 µg/kg (doses of ouabain indicating that maximal effects were achieved. Although the magnitude of natriuresis after maximal doses of ouabain is partially dependent upon the distribution of the Na⁺ load along the nephron and is not constant for various conditions of hydration, it is clear that mechanism(s) for the reabsorption of glomerular filtrate other than those sensitive to ouabain exist in the kidney.