Prostaglandin E1 at clinically relevant concentrations inhibits aggregation of platelets under synergic interaction with endothelial cells

Background: The inhibitory effect of prostaglandin E-1 (PGE(1)) on platelet aggregation is considered an important characteristic of this agent. However, the concentration of PGE(1) to inhibit aggregation in vitro is higher than those of clinical use (1 ng/ml). To clarify whether PGE(1) at clinically relevant concentrations inhibits aggregation under synergic action with endothelial cell-derived factors (nitric oxide and prostacyclin), we evaluated the minimum effective concentration of PGE(1) to enhance the anti-aggregating activity of endothelial cells. Methods: Inhibitory effects of PGE(1) and/or the incubation buffer from cultured porcine aortic endothelial (PAE) cells on human platelet aggregation induced by 2 mug/ml collagen were examined by turbidimetry. Results: PGE(1) concentration-dependently (>3 ng/ml) inhibited aggregation: the incubation buffer from PAE cells stimulated by bradykinin also inhibited aggregation. Bradykinin concentration-dependently increased the anti-aggregating activity of the PAE incubation buffer. The half-maximum effective concentration of bradykinin to inhibit aggregation (95.4+/-22.3 nM) was significantly decreased to 10.3+/-2.5 nM by 0.1 ng/ml PGE(1) and to 0.9+/-0.5 nM by 1 ng/ml PGE(1), respectively. These indicated that PGE(1) (=0.1 ng/ml) inhibits aggregation through synergism with endothelial cells. The synergic effect of PGE(1) and the anti-aggregating activity of the PAE cells preincubated with 10 muM indomethacin for 30 min was more potent than that of these cells preincubated with 1 mM N-G-nitro-L-arginine methyl ester. This suggested that the interaction of PGE(1) with endothelial cell-derived nitric oxide is more powerful than that with endothelial cell-derived prostacyclin. Conclusions: Prostaglandin E-1 (=0.1 ng/ml) inhibited platelet aggregation under synergic interaction with endothelial cells.