Kritz H, Schmid P, Keiler A, O'Grady J, Sinzinger H
Wilhelm Auerswald Atherosclerosis Research Group (ASF), Vienna, Austria.
Thromb Res. 1995 Dec 15;80(6):483-9. doi: 10.1016/0049-3848(95)00203-0.
PGI2- and TXA2-synthesis from vascular tissue samples derived from cultured (endothelial and smooth muscle) cells, rabbit aorta and human bypass surgery were determined using specific radioimmunoassays for the stable derivatives (6-oxo-PGF1a and TXB2, respectively) of these compounds. Cultured cells were incubated in presence of isradipine, rabbits were pretreated for 4 weeks receiving 0.3 mg isradipine/kg*day, while patients were on isradipine (5-10 mg total dose/day, per os twice daily) since 6-19 weeks. In presence of isradipine, cultured cells produced significantly (p < 0.01) more 6-oxo-PGF1a and significantly less TXB2 (p < 0.05). 6-oxo-PGF1a-formation in rabbit aorta was significantly (p < 0.01) higher in isradipine treated normocholesterolemic animals while no significant changes were seen in isradipine treated hypercholesterolemic animals. TXB2 was significantly (p < 0.01) depressed in the abdominal and the thoracic aortic segment of isradipine treated hypercholesterolemic animals and was not significantly influenced in isradipine treated normocholesterolemic animals. Similarly, PGI2-synthesis in human arterial specimen was significantly (p < 0.01) enhanced as compared to the untreated controls. These findings indicate a beneficial behaviour of isradipine on vascular wall eicosanoid profile, which may contribute to a variety of antiatherosclerotic actions at the vascular wall level and to an improvement in hemostatic balance already described.
使用针对这些化合物的稳定衍生物(分别为6-氧代前列环素F1α和血栓素B2)的特异性放射免疫分析法,测定了来自培养的(内皮和平滑肌)细胞、兔主动脉和人体搭桥手术的血管组织样本中前列环素2(PGI2)和血栓素A2(TXA2)的合成。将培养的细胞在异搏定存在的情况下进行孵育,给兔子预处理4周,给予0.3毫克异搏定/千克·天,而患者自6至19周以来一直服用异搏定(总剂量5 - 10毫克/天,口服,每日两次)。在异搏定存在的情况下,培养的细胞产生的6-氧代前列环素F1α显著增多(p < 0.01),而血栓素B2显著减少(p < 0.05)。在接受异搏定治疗的正常胆固醇血症动物中,兔主动脉中的6-氧代前列环素F1α形成显著增加(p < 0.01),而在接受异搏定治疗的高胆固醇血症动物中未观察到显著变化。在接受异搏定治疗的高胆固醇血症动物的腹主动脉和胸主动脉段中,血栓素B2显著降低(p < 0.01),而在接受异搏定治疗的正常胆固醇血症动物中未受到显著影响。同样,与未处理的对照相比,人体动脉标本中的前列环素2合成显著增强(p < 0.01)。这些发现表明异搏定对血管壁类花生酸谱具有有益作用,这可能有助于在血管壁水平发挥多种抗动脉粥样硬化作用,并有助于改善已描述的止血平衡。