Effects of Bay k 8644, a Dihydropyridine Analog, on [H]Nitrendipine Binding to Canine Cardiac Sarcolemma and the Relationship to a Positive Inotropic Effect

Equilibrium dissociation constants of Bay k 8644, a calcium agonist, and nitrendipine, a calcium antagonist, were determined in canine cardiac sarcolemma. The equilibrium dissociation constant for Bay k 8644 was compared to the concentration that produced a fifty percent increase, and the equilibrium dissociation constant for nitrendipine was compared to the concentration that produced a fifty percent decrease, in contractile force in canine heart trabecular muscle. Both saturation and inhibition binding data suggest that Bay k 8644 and nitrendipine bind to and compete for a high affinity dihydropyridine-binding site present in isolated cardiac sarcolemma preparations. The equilibrium dissociation constant (7-10 nM) and concentration that produced a fifty percent increase in contractile force in the canine trabecular muscle (30 ± 8 nM) of Bay k 8644 were in a similar concentration range, but the equilibrium dissociation constant (0.29 ± 0.025 nM) of nitrendipine binding was more than a thousand-fold lower than the concentration that produced a fifty percent decrease in contractile force in canine trabecular muscle (613 ± 109 run). These data suggest that binding of Bay k 8644 to high affinity binding sites is pharmacologically relevant, and is related to a positive inotropic effect. (Circ Res 55: 549-553, 1984)