title: 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 10 min. 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.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Furui
authors.forename: T
authors.initials: T
authors.lastname: Furumichi
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Yamauchi
authors.forename: M
authors.initials: M
authors.lastname: Yokota
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000244:Adenosine Diphosphate / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D001854:Bone Marrow Cells; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D009529:Nicardipine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D000244:Adenosine Diphosphate; D003094:Collagen; D014700:Verapamil; D009529:Nicardipine; D011464:Epoprostenol; D013917:Thrombin; D004110:Diltiazem; D001241:Aspirin