Effects of carbacyclin analogue (CS-570) and dibutyryl cAMP (Actosin) on platelet aggregation and prostacyclin generation of cultured human vascular endothelial cells.

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The effects of a new carbacyclin analogue (CS-570) and dibutyryl cAMP [db-cAMP (Actosin)] on the aggregation of the human platelet prostacyclin (PGI2) generation of cultured human vascular endothelial cells were investigated. The endothelial cells were isolated from human umbilical cord veins and cultured by the modified method of jaffe et al.CS-570 or db-cAMP inhibited ADP or collagen induced platelet aggregation and thromboxane B2 (TXB2) generation in dose dependent manners. They increased cAMP concentration, but they had no effect on cGMP levels. These results suggested that the inhibition of platelet aggregation by these reagents might be due to the elevation of cAMP levels and inhibition of TXB2 generation.In the endothelial cells, CS-570 and db-cAMP increased intracellular cAMP concentration, while CS-570 enhanced PGI2 generation of endothelial cells and db-cAMP decreased it. Both of them had no effect on cGMP levels.From these results, it was concluded that CS-570, which increased intrinsic PGI2 generation of endothelial cells, was considered to be more beneficial for anticoagulant therapy than Actosin. Because Actosin brought the decrease of PGI2 generation in the endothelial cells.
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