Weiss K
Atheroskleroseforschungsgruppe, Wien.
Wien Klin Wochenschr. 1988 Nov 4;100(21):718-20.
The aim of the study was to investigate the influence of calcium blockers on the prostaglandin system of blood platelets and the vessel wall with respect to a possible beneficial effect on atherosclerosis. The influence of diltiazem, isradipine, nifedipine and verapamil was examined on ADP- and collagen-induced in vitro platelet aggregation, platelet malondialdehyde formation and other platelet function tests. All the calcium blockers investigated inhibited platelet activation in a dose-dependent manner, isradipine being the most effective. Malondialdehyde formation (measured photometrically) and thromboxane (TX) B2 production were decreased too. Vascular tissue PG12 formation was investigated in rat aortic rings (6-oxo-PGF1 alpha-RIA). PG12 formation was enhanced by all the calcium blockers investigated (p less than 0.01), isradipine again having the most pronounced effect. Platelet adenylate cyclase was stimulated by diltiazem only (RIA, HPLC). Ex vivo ADP-, collagen- and epinephrine-induced platelet aggregation and serum TX were studied 90 minutes after ingestion to diltiazem (60 mg), nifedipine (20 mg) and verapamil (40 mg). ADP- and epinephrine-induced platelet aggregation (19-36%) and serum TX were reduced significantly (p less than 0.01), but collagen-induced aggregation was not significantly affected. These results suggest a possibly beneficial effect of calcium blockers on atherosclerosis via the prostaglandin system.
本研究的目的是探讨钙通道阻滞剂对血小板和血管壁前列腺素系统的影响，以及其对动脉粥样硬化可能的有益作用。研究了地尔硫䓬、伊拉地平、硝苯地平和维拉帕米对二磷酸腺苷（ADP）和胶原诱导的体外血小板聚集、血小板丙二醛形成及其他血小板功能测试的影响。所有研究的钙通道阻滞剂均以剂量依赖方式抑制血小板活化，其中伊拉地平最为有效。丙二醛形成（通过光度法测量）和血栓素（TX）B2生成也减少。在大鼠主动脉环中研究了血管组织前列环素（PGI2）的形成（6-氧代前列腺素F1α放射免疫分析）。所有研究的钙通道阻滞剂均增强了PGI2的形成（p<0.01），伊拉地平的作用最为显著。仅地尔硫䓬刺激血小板腺苷酸环化酶（放射免疫分析、高效液相色谱法）。在摄入地尔硫䓬（60mg）、硝苯地平（20mg）和维拉帕米（40mg）90分钟后，研究了离体条件下ADP、胶原和肾上腺素诱导的血小板聚集以及血清TX。ADP和肾上腺素诱导的血小板聚集（19%-36%）及血清TX显著降低（p<0.01），但胶原诱导的聚集未受到显著影响。这些结果表明钙通道阻滞剂可能通过前列腺素系统对动脉粥样硬化产生有益作用。
