Re-evaluation of the relationship between the positive inotropic effect of ouabain and its inhibitory effect on (Na+ + K+)-dependent adenosine triphosphatase in rabbit and dog hearts.
Previous studies have shown that in the ouabain-exposed rabbit heart, although positive inotropy and inhibition of (Na+ + K+)-dependent adenosine triphosphatase are induced concomitantly, the extent of inhibition of the enzyme remains constant when positive inotropy is washed out; and in the dog heart, if positive inotropy without arrhythmias is induced by ouabain, inhibition of the enzyme is not detected. The purpose of this work was the re-evaluation of these previous findings. Rapid recovery of the enzyme from small tissue samples was achieved by homogenization in 1 M KCl and centrifugation. When the enzyme was prepared by this method from ouabain-exposed rabbit and dog hearts, ouabain remained bound to the enzyme. The extent of inhibition of the enzyme was measured by the fluorimetric assay of K+-dependent 3-O-methylfluorescein phosphatase before and after removal of bound ouabain. Correlation between the extent of inhibition of this activity and that of (Na+ + K+)-dependent adenosine triphosphatase activity was established. Utilizing these refined methods, the following results were obtained. In the rabbit heart, positive inotropy and enzyme inhibition occurred concomitantly. Washout of the effect resulted in partial reactivation of the enzyme. In the dog heart, the previous findings were confirmed. The results are not inconsistent with the hypothesis that enzyme inhibition is the cause of the positive inotropic effects. They do suggest, however, the need for further testing of the hypothesis.
D000818:Animals; D004285:Dogs; D004355:Drug Stability; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013045:Species Specificity; D013268:Stimulation, Chemical; D013997:Time Factors
D010042:Ouabain; D011189:Potassium Chloride; D010744:Phosphoric Monoester Hydrolases; D000254:Sodium-Potassium-Exchanging ATPase