Inhibitory Effects of Endothelial Cells and Calcium Channel Blockers on Platelet Aggregation

Abstract

This study examined the effects of human umbilical vein endothelial cells (ECs) and calcium channel blockers (Ca²⁺ blockers), diltiazem, verapamil, and nicardipine, on platelet aggregation in vitro. ECs markedly inhibited the platelet aggregation induced by ADP, collagen, thromboxane A₂ (TXA₂), or thrombin. When platelets were incubated with ECs, the antiaggregatory activity reached a plateau within 5 to 10min. As the number of ECs added to the platelet-rich plasma was increased, platelet aggregation declined progressively. The antiaggregatory activity of ECs was attenuated considerably by the addition of aspirin. All three Ca²⁺ blockers inhibited platelet aggregation in a dose-dependent manner. The combination of ECs and a Ca2+ blocker resulted in more potent inhibition of platelet aggregation than either alone, but the effects were not synergistic. Both ECs and Ca²⁺ blockers inhibited the synthesis of TXA2 during platelet aggregation. However, Ca²⁺ blockers did not significantly influence the production of prostaglandin I₂ (PGI₂) by ECs during incubation and aggregation. These results suggest that PGI₂ is an important factor in endothelial antiaggregatory activity. Ca²⁺ blockers directly inhibit platelet aggregation by suppressing TXA₂ formation, but do not appear to enhance the antiaggregatory activity of ECs.