T Koga1, T Az-ma, O Yuge. 1. Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Hiroshima University, Japan.
Abstract
BACKGROUND: The inhibitory effect of prostaglandin E1 (PGE1) on platelet aggregation is considered an important characteristic of this agent. However, the concentration of PGE1 to inhibit aggregation in vitro is higher than those of clinical use (1 ng/ml). To clarify whether PGE1 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 PGE1 to enhance the anti-aggregating activity of endothelial cells. METHODS: Inhibitory effects of PGE1 and/or the incubation buffer from cultured porcine aortic endothelial (PAE) cells on human platelet aggregation induced by 2 micro g/ml collagen were examined by turbidimetry. RESULTS: PGE1 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 PGE1 and to 0.9+/-0.5 nM by 1 ng/ml PGE1, respectively. These indicated that PGE1 (=0.1 ng/ml) inhibits aggregation through synergism with endothelial cells. The synergic effect of PGE1 and the anti-aggregating activity of the PAE cells preincubated with 10 micro M indomethacin for 30 min was more potent than that of these cells preincubated with 1 mM NG-nitro-L-arginine methyl ester. This suggested that the interaction of PGE1 with endothelial cell-derived nitric oxide is more powerful than that with endothelial cell-derived prostacyclin. CONCLUSION: Prostaglandin E1 (=0.1 ng/ml) inhibited platelet aggregation under synergic interaction with endothelial cells.
BACKGROUND: The inhibitory effect of prostaglandin E1 (PGE1) on platelet aggregation is considered an important characteristic of this agent. However, the concentration of PGE1 to inhibit aggregation in vitro is higher than those of clinical use (1 ng/ml). To clarify whether PGE1 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 PGE1 to enhance the anti-aggregating activity of endothelial cells. METHODS: Inhibitory effects of PGE1 and/or the incubation buffer from cultured porcine aortic endothelial (PAE) cells on humanplatelet aggregation induced by 2 micro g/ml collagen were examined by turbidimetry. RESULTS:PGE1 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 PGE1 and to 0.9+/-0.5 nM by 1 ng/ml PGE1, respectively. These indicated that PGE1 (=0.1 ng/ml) inhibits aggregation through synergism with endothelial cells. The synergic effect of PGE1 and the anti-aggregating activity of the PAE cells preincubated with 10 micro M indomethacin for 30 min was more potent than that of these cells preincubated with 1 mM NG-nitro-L-arginine methyl ester. This suggested that the interaction of PGE1 with endothelial cell-derived nitric oxide is more powerful than that with endothelial cell-derived prostacyclin. CONCLUSION:Prostaglandin E1 (=0.1 ng/ml) inhibited platelet aggregation under synergic interaction with endothelial cells.