Drummer C, Valta-Seufzer U, Karrenbrock B, Heim J M, Gerzer R
Medizinische Klinik, Klinikum Innenstadt der Universität, München, Germany.
Eur Heart J. 1991 Apr;12(4):541-9. doi: 10.1093/oxfordjournals.eurheartj.a059936.
The purpose of the present work was to investigate the ex vivo platelet-inhibiting properties of the nitric oxide-containing vasodilator, molsidomine, and the organic nitrate, isosorbide-5-mononitrate, in comparison with placebo. Ex vivo platelet aggregation in 11 healthy volunteers was measured before, as well as 30 and 60 min after, the intake of either 4 mg molsidomine, 20 mg isosorbide-5-mononitrate (ISMN) or placebo in a randomized double-blind fashion. The release of thromboxane was also determined. Threshold doses of platelet-activating factor (PAF) to induce irreversible aggregation were significantly increased by 100 and 120% 30 and 60 min after molsidomine. Slopes of aggregation curves (aggregation induced with 50 and 200 nM PAF) were significantly reduced after molsidomine (P less than 0.01). Small platelet-inhibiting effects were also observed after ISMN and after placebo intake. The release of thromboxane was not influenced when platelets were maximally stimulated either during clotting of whole blood or during aggregation of platelet-rich plasma with a high dose of PAF. Thromboxane release with a low dose of PAF was reduced 30 and 60 min after drug intake, independent of whether molsidomine, ISMN or placebo was applied. The data indicate that the usual clinical doses of molsidomine, but not of ISMN inhibit platelet aggregation in healthy man.
本研究的目的是对比含一氧化氮的血管扩张剂莫索尼定和有机硝酸盐5-单硝酸异山梨酯与安慰剂相比的体外血小板抑制特性。以随机双盲方式，对11名健康志愿者在摄入4毫克莫索尼定、20毫克5-单硝酸异山梨酯（ISMN）或安慰剂之前以及之后30和60分钟测量体外血小板聚集情况。同时也测定了血栓素的释放。莫索尼定摄入后30和60分钟，诱导不可逆聚集的血小板激活因子（PAF）阈值剂量显著增加了100%和120%。莫索尼定摄入后，聚集曲线斜率（由50和200 nM PAF诱导的聚集）显著降低（P小于0.01）。ISMN和安慰剂摄入后也观察到了较小的血小板抑制作用。当全血凝血过程中或用高剂量PAF使富含血小板血浆聚集过程中血小板受到最大刺激时，血栓素的释放未受影响。药物摄入后30和60分钟，低剂量PAF诱导的血栓素释放减少，无论应用的是莫索尼定、ISMN还是安慰剂。数据表明，莫索尼定的常用临床剂量可抑制健康男性的血小板聚集，而ISMN则不然。
