Effects of progesterone derivatives on sodium pump activity and force of myocardial contraction in isolated guinea pig heart.

A progesterone derivative, chlormadinone acetate, has been reported to inhibit isolated Na,K-ATPase, to increase intracellular sodium, to decrease the force of myocardial contraction and to antagonize the positive inotropic action of ouabain. Because several inhibitors of isolated Na,K-ATPase fail to interact with the sodium pump in intact cells, two progesterone derivatives, chlormadinone acetate and megestrol acetate were examined for their effects on Na,K-ATPase, sodium pump activity and the force of contraction in isolated guinea pig atria. Both megestrol acetate and chlormadinone acetate inhibited specific (ATP-dependent) 3H-ouabain binding to Na,K-ATPase isolated from guinea pig brain or heart, with a corresponding inhibition of enzyme activity. The effects on Na,K-ATPase obtained from brain were more pronounced than that obtained from heart. The inhibitory effect of megestrol acetate was partially antagonized by K+. In electrically stimulated left atrial muscle preparations, neither compound affected ouabain-sensitive 42K+ uptake. Additionally, these compounds failed to affect the force of myocardial contraction or to influence the positive inotropic action of ouabain. These data fail to support the contention that inhibition of the sarcolemmal sodium pump is unrelated to the ouabain-induced increase in the force of myocardial contraction.