Relationship between the positive inotropic effect of ouabain and its inhibitory effects on Na+, K+ -ATPase and active transport of Rb+ in the dog heart.
Two previous reports have indicated that in the dog if sustained positive inotropy without arrhythmias is induced by ouabain infusion, inhibition of myocardial Na+, K+-activated adenosine triphosphatase is not observed. Another previous study has shown that in similar experiments induction of sustained inotropy is accompanied by inhibition of the active uptake of Rb+. To resolve the apparent inconsistencies between these findings, we repeated the experiments and measured the inhibition of the enzyme and the inhibition of Rb+ uptake after the induction of sustained inotropy with ouabain. Utilizing three different ouabain dosage regimens in open-chested dogs, we obtained three different quasi-steady state plasma levels of ouabain. At the highest level, ouabain toxicity accompanied by enzyme inhibition and inhibition to RB+ uptake was observed. With the intermediate levels, positive inotropy without significant toxicity was also accompanied by enzyme inhibition and the inhibition of Rb+ uptake. At the lowest ouabain plasma levels, sustained positive inotropy without significant inhibition of either enzyme activity or +b+ uptake was obtained. The data indicate that in this preparation either a small degree of enzyme inhibition, which is difficult to detect is sufficient to produce pronounced positive inotropy, or that the inhibition of the enzyme is not required for the induction of positive inotropy.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010042:Ouabain / Q000097:blood / Q000494:pharmacology*; D011955:Receptors, Drug / Q000378:metabolism; D012413:Rubidium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical
D011955:Receptors, Drug; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium