Block H U, Heinroth I, Giessler C, Pönicke K, Mentz P, Zehl U, Rettkowski W, Dunemann A, Förster W
Biomed Biochim Acta. 1983;42(2-3):283-99.
The influence of the antianginal drug trapidil on the biosynthesis of thromboxane A2 (TXA2) and/or prostacyclin (PGI2), metabolites of arachidonic acid (AA), was investigated in rabbit and human platelet rich plasma (PRP), in homogenates of rabbit spleen and of rat lung and in aortic preparations of rats and rabbits, respectively. Trapidil showed a marked inhibition of the AA-induced aggregation and TXA2 biosynthesis in rabbit and human PRP. The TXA2 inhibition by trapidil was not demonstrable in damaged platelets and seems to require intact cells. In homogenates of rat lungs, trapidil remained without effect on the TXA2 and PGI2 synthesis. In rabbit spleen homogenates the drug induced an inhibition of the formation of both AA metabolites. In contrast to Japanese authors we could not observe any increase in PGI2 release in rat aortic preparation. The PGI2 release from isolated perfused guinea pigs hearts was enhanced; on the other hand, the PGI2 efflux from rabbit hearts remained unchanged. The antiaggregatory effect of PGI2 on the ADP-induced aggregation was strengthened by trapidil, showing an overadditive effect in rabbit PRP. The aggregation inducing effect of the prostaglandin endoperoxide analog U-46619 was inhibited by trapidil. A possible clinical significance of the inhibitions of the synthesis and effect of TXA2 for therapy of ischemic heart disease is discussed.
分别在兔和人富含血小板血浆（PRP）、兔脾脏匀浆、大鼠肺匀浆以及大鼠和兔的主动脉制剂中，研究了抗心绞痛药物曲匹地尔对花生四烯酸（AA）代谢产物血栓素A2（TXA2）和/或前列环素（PGI2）生物合成的影响。曲匹地尔对兔和人PRP中AA诱导的聚集和TXA2生物合成有显著抑制作用。曲匹地尔对TXA2的抑制作用在受损血小板中未得到证实，似乎需要完整细胞。在大鼠肺匀浆中，曲匹地尔对TXA2和PGI2的合成无影响。在兔脾脏匀浆中，该药物可抑制两种AA代谢产物的形成。与日本作者不同，我们在大鼠主动脉制剂中未观察到PGI2释放增加。曲匹地尔可增强PGI2对ADP诱导聚集的抗聚集作用，在兔PRP中显示出超相加效应。曲匹地尔可抑制前列腺素内过氧化物类似物U-46619的聚集诱导作用。讨论了抑制TXA2合成和作用对缺血性心脏病治疗的可能临床意义。
