In vivo interaction of prostacyclin with an inhibitor of cyclic nucleotide phosphodiesterase, HL 725
In vivo interaction of prostacyclin with an inhibitor of cyclic nucleotide phosphodiesterase, HL 725
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前列环素与环核苷酸磷酸二酯酶抑制剂 HL 725 的体内相互作用
DOI：
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发表时间：
1985
影响因子：
7.3
通讯作者：
J. Smith
中科院分区：
文献类型：
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作者：
H. Darius;A. M. Lefer;I. Leprán;J. Smith
1 Prostacyclin （PGI2）通过刺激腺苷酸环化酶使血小板失活，其作用可以通过在体外同时抑制环AMP磷酸二酯酶而增强。在静脉注射胶原的全身血小板活化模型中，研究了合成PGI2与强效磷酸二酯酶抑制剂HL 725的相互作用。通过连续在线测量循环血小板计数来评估血小板聚集形成。注射胶原蛋白的兔接受载体后，循环血小板计数下降30±3%。输注PGI2（0.05、0.1和0.75 μg kg−1 min−1）剂量依赖性地抑制了这种降低。hl725（0.5、1和3 μg kg−1 min−1）的作用虽小，但效果显著。PGI2和HL 725分别在0.25 + 1.0和0.1 + 0.5 μg kg - 1 min - 1作用下对血小板聚集形成的抑制作用大于单独使用时，其抑制作用与PGI2在0.75 μg kg - 1 min - 1作用下的抑制作用相当。胶原诱导急性平均动脉血压（MABP）下降，PGI2、HL 725及其联合抑制MABP的下降。PGI2和HL 725联合输注在胶原蛋白前产生的MABP下降比单独使用任何一种化合物时都要大。因此，PGI2和磷酸二酯酶抑制剂HL 725在体内相互作用，抑制血小板聚集和降低MABP。
1 Prostacyclin (PGI2) inactivates platelets by stimulation of adenylate cyclase, and its effect can be potentiated in vitro by simultaneous inhibition of cyclic AMP phosphodiesterase. 2 The interaction of synthetic PGI2 and the potent phosphodiesterase inhibitor HL 725 was studied in a model of systemic platelet activation by intravenous injection of collagen. Platelet aggregate formation was evaluated by continuous on‐line measurement of the circulating platelet count. 3 Collagen injection in rabbits receiving vehicle caused a 30 ± 3% decrease in the circulating platelet count. Infusion of PGI2 (0.05, 0.1 and 0.75 μg kg−1 min−1) dose‐dependently inhibited this decrease. HL 725 (0.5, 1 and 3 μg kg−1 min−1) caused a slight but significant effect. 4 Combinations of PGI2 and HL 725, respectively, at 0.25 + 1.0 and 0.1 + 0.5 μg kg−1 min−1 inhibited platelet aggregate formation to a greater extent than when either substance was used alone and produced a comparable inhibition to PGI2 at 0.75 μg kg−1 min−1. 5 Collagen induced an acute fall in the mean arterial blood pressure (MABP) which also was inhibited by PGI2, HL 725 and their combinations. 6 The infusion of a combination of PGI2 and HL 725 before collagen produced a decrease in the MABP which was greater than when either compound was used on its own. 7 Thus, PGI2 and the phosphodiesterase inhibitor HL 725 interact in vivo to inhibit platelet aggregation and lower MABP.