ISRADIPINE INCREASES VASCULAR PROSTAGLANDIN I-2-FORMATION WHILE THE THROMBOXANE B-2-SYNTHESIS IS DIMINISHED

PGI(2)- and TXA(2)-synthesis from vascular tissue samples derived from cultured (endothelial and smooth muscle) cells, rabbit aorta and huma n bypass surgery were determined using specific radioimmunoassays for the stable derivatives (6-oxo-PGF(1a) and TXB(2), respectively) of the se compounds. Cultured cells were incubated in presence of isradipine, rabbits were pretreated for 4 weeks receiving 0.3 mg isradipine/kg da y, while patients were on isradipine (5-10 mg total dose/day, per os t wice daily) since 6-19 weeks. In presence of isradipine, cultured cell s produced significantly (p < 0.01) more 6-oxo-PGF(1a) and significant ly less TXB, (p < 0.05). 6-oxo-PGF(1a)-formation in rabbit aorta was s ignificantly (p < 0.01) higher in isradipine treated normocholesterole mic animals while no significant changes were seen in isradipine treat ed hypercholesterolemic animals. TXB(2) was significantly (p < 0.01) d epressed in the abdominal and the thoracic aortic segment of isradipin e treated hypercholesterolemic animals and was not significantly influ enced in isradipine treated normocholesterolemic animals. Similarly, P GI(2)-synthesis in human arterial specimen was significantly (p < 0.01 ) enhanced as compared to the untreated controls. These findings indic ate a beneficial behaviour of isradipine on vascular wall eicosanoid p rofile, which may contribute to a variety of antiatherosclerotic actio ns at the vascular wall level and to an improvement in hemostatic bala nce already described.