Prostaglandin E1 at clinically relevant concentrations inhibits aggregation of platelets 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 relev...
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Published in | Acta anaesthesiologica Scandinavica Vol. 46; no. 8; pp. 987 - 993 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Munksgaard International Publishers
01.09.2002
Blackwell |
Subjects | |
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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 µg/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 µM 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. |
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AbstractList | 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 µg/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 µM 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. 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. 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. 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. Prostaglandin E1 (=0.1 ng/ml) inhibited platelet aggregation under synergic interaction with endothelial cells. |
Author | Yuge, O. Koga, T. Az-Ma, T. |
Author_xml | – sequence: 1 givenname: T. surname: Koga fullname: Koga, T. organization: Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Hiroshima University, Minami-ku, and – sequence: 2 givenname: T. surname: Az-Ma fullname: Az-Ma, T. organization: Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Hiroshima University, Minami-ku, and – sequence: 3 givenname: O. surname: Yuge fullname: Yuge, O. organization: Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Hiroshima University, Minami-ku, and |
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Keywords | Human Cell culture Endothelial cell Prostaglandin I2 Prostaglandin E1 In vitro Synergism Antiplatelet agent Pig Aggregation Vertebrata Platelet Mammalia Animal Nitric oxide Artiodactyla Ungulata |
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References_xml | – volume: 40 start-page: 273 year: 1995 end-page: 276 article-title: Dose proportional pharmacokinetics of alprostadil (prostaglandin E ) in healthy volunteers following intravenous infusion publication-title: Br J Clin Pharmacol – volume: 50 start-page: 749 year: 1988 end-page: 755 article-title: Comparable effect of prostaglandin E in decreasing in vivo platelet deposition on human lesion sites after intravenous and intraarterial application publication-title: Thromb Res – volume: 45 start-page: 207 year: 1992 end-page: 210 article-title: Synergism between PGE ‐metabolites (13,14‐dihydro‐prostaglandin E , 15‐ keto prostaglandin E , 15‐keto‐13,14‐dihydro‐prostaglandin E ) and nitric oxide (NO) on platelet aggregation publication-title: Prostaglandins Leukot Essent Fatty Acids – volume: 137 start-page: 5 year: 1988 end-page: 12 article-title: Pulmonary extraction and pharmacokinetics of prostaglandin E during continuous intravenous infusion in patients with adult respiratory distress syndrome publication-title: Am Rev Respir Dis – volume: 83 start-page: 374 year: 1995 end-page: 381 article-title: Inhibitory effect of lidocaine on cultured porcine aortic endothelial cell‐dependent anti‐aggregation of platelets publication-title: Anesthesiology – volume: 43 start-page: 109 year: 1991 end-page: 142 article-title: Nitric oxide. 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Early and long‐term results publication-title: Vasa – volume: 275 start-page: H1482 year: 1998 end-page: H1488 article-title: Endothelial dysfunction in human intramyocardial small arteries in atherosclerosis and hypercholesterolemia publication-title: Am J Physiol – volume: 65 start-page: 796 year: 1989 end-page: 804 article-title: Synergistic disaggregation of platelets by tissue‐type plasminogen activator, prostaglandin E , and nitroglycerin publication-title: Circ Res – start-page: 601 year: 1996: end-page: 616 – volume: 29 start-page: 314 year: 1992 end-page: 320 article-title: Continuous intraarterial infusion of prostaglandin E and heparin to extend and improve the survival of pedicled musculocutaneous flaps through unusual routes: a clinical preliminary report publication-title: Ann Plast Surg – volume: 126 start-page: 1462 year: 1999 end-page: 1470 article-title: Cytosolic Ca movements of endothelial cells exposed to reactive oxygen intermediates: role of hydroxyl radical‐mediated redox alteration of cell‐membrane Ca channels publication-title: Br J Pharmacol – volume: 113 start-page: 385 year: 1994 end-page: 388 article-title: Antiplatelet activities of FK409, a new spontaneous NO releaser publication-title: Br J Pharmacol – volume: 335 start-page: 627 year: 1990 end-page: 628 article-title: Synergistic effect of prostaglandin E and isosorbide dinitrate in peripheral vascular disease publication-title: Lancet – volume: 281 start-page: 1031 year: 1980 end-page: 1034 article-title: Treatment of vasospastic disease with prostaglandin E publication-title: Br Med – volume: 18 start-page: 359 year: 1985 end-page: 366 article-title: Antihypertensive activity and metabolic rate of prostaglandin E in surgical patients under general anesthesia publication-title: Prostaglandins Leukot Med – volume: 289 start-page: 455 year: 1995 end-page: 461 article-title: Synergistic interaction of adenylate cyclase activators and nitric oxide donor SIN‐1 on platelet cyclic AMP publication-title: Eur J Pharmacol – volume: 62 start-page: 915 year: 1996 end-page: 922 article-title: Endothelial cell injury in cardiovascular surgery publication-title: Ann Thorac Surg – volume: 71 start-page: 217 year: 1993 end-page: 225 article-title: Effect of prostaglandin (PG) E and its initial metabolites on neutrophil‐induced inhibition of human platelet aggregation publication-title: Thromb Res – volume: 92 start-page: 181 year: 1987 end-page: 187 article-title: Comparative pharmacology of endothelium‐derived relaxing factor, nitric oxide and prostacyclin in platelets publication-title: Br J Pharmacol – volume: 62 start-page: 299 year: 1991 end-page: 304 article-title: Interaction between prostaglandin E and nitric oxide (NO) publication-title: Thromb Res – volume: 46 start-page: 275 year: 1994 end-page: 277 article-title: Metabolism and pharmacokinetics of prostaglandin E administered by intravenous infusion in human subjects publication-title: Eur J Clin Pharmacol |
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Snippet | Background: The inhibitory effect of prostaglandin E1 (PGE1) on platelet aggregation is considered an important characteristic of this agent. However, the... The inhibitory effect of prostaglandin E1 (PGE1) on platelet aggregation is considered an important characteristic of this agent. However, the concentration of... |
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StartPage | 987 |
SubjectTerms | Alprostadil - pharmacology Animals Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Cells, Cultured Dose-Response Relationship, Drug Drug Synergism Endothelial cells Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Epoprostenol - pharmacology Medical sciences NG-Nitroarginine Methyl Ester - pharmacology nitric oxide Nitric Oxide - pharmacology Nitric Oxide Synthase - antagonists & inhibitors Pharmacology. Drug treatments platelet aggregation Platelet Aggregation - drug effects Platelet Aggregation Inhibitors - pharmacology prostacyclin prostaglandin E1 Swine synergic effect |
Title | Prostaglandin E1 at clinically relevant concentrations inhibits aggregation of platelets under synergic interaction with endothelial cells |
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