Prostaglandin E 1 at clinically relevant concentrations inhibits aggregation of platelets under synergic interaction with endothelial cells

• Published in: Acta anaesthesiologica Scandinavica Vol. 46; no. 8; pp. 987 - 993
• Main Authors: Koga, T., Az‐Ma, T., Yuge, O.
• Format: Journal Article
• Language: English
• Published: 01.09.2002
• ISSN: 0001-5172; 1399-6576
• DOI: 10.1034/j.1399-6576.2002.460810.x

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 µg/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 µM 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. Conclusion: Prostaglandin E 1 (=0.1 ng/ml) inhibited platelet aggregation under synergic interaction with endothelial cells.