Effect of the Calcium-Entry Blocking Agent Nifedipine on Activation of Human Platelets and Comparison with Verapamil

Abstract

The effects of the calcium-entry blocking agent nifedipine on the activation of human platelets by various agonists has been studied and compared with verapamil. Like verapamil, nifedipine inhibited platelet aggregation and secretion caused by collagen, the second phase of ADP-induced aggregation, and aggregation caused by the ionophore A23187. Both agents inhibited the formation of TXB2 from endogenous arachidonate, whereas only nifedipine inhibited platelet aggregation and decreased TXB2 formation caused by exogenous arachidonate without inhibiting uptake. These results indicate that both calcium-blocking agents may be inhibiting the release of arachidonate in platelets by phospholipases, and that nifedipine also inhibits the formation and action of thromboxane A2 in platelets. Epinephrine-induced aggregation was inhibited by low concentrations of verapamil while nifedipine only inhibited aggregation by epinephrine at much higher concentrations. It is suggested that low concentrations of verapamil inhibit epinephrine-induced aggregation by interacting with platelet alpha-adrenergic receptors, and that higher concentrations of both calcium-blocking agents inhibit platelet responses to other aggregating agents by preventing intracellular calcium mobilization.