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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Evans, T. W. Cranshaw, J. H. Mitchell, J. A. |
| Description | Author Affiliation: Cranshaw JH ( Unit of Critical Care Medicine, Royal Brompton Hospital, NHLI Division of Imperial College School of Medicine, Sydney Street, London SW3 6NP.) |
| Abstract | We tested the effects of 11 commercially-available isoprostanes on platelet aggregation directly or when triggered by the thromboxane receptor agonist U46619 or collagen in healthy human citrated blood using a whole blood aggregometer. None of the isoprostanes tested triggered aggregation alone, nor facilitated aggregation by a sub-threshold dose of U46619 or collagen. Five isoprostanes inhibited aggregation (rank order of potency 8-iso PGE(1)>8-iso PGE(2)>8-iso PGF(2alpha)>8-iso PGF(3alpha)>8-iso-13,14-dihydro-15-keto PGF(2alpha)). Blood incubated with LPS to induce a gross inflammatory response exhibited a time dependent (2 - 12 h) reduction in aggregation to U46619 but maintained a consistent response to collagen. Under these conditions, as in control blood, none of the isoprostanes tested induced aggregation. In fact, the inhibitory actions of isoprostanes on U46619-induced aggregation were enhanced in blood treated with LPS. L-NAME inhibited aggregation induced by U46619 in fresh blood and in blood treated with LPS. In the presence of L-NAME, (with or without LPS) none of the isoprostanes tested induced aggregation but retained their inhibitory action. Thus, in human whole blood the action of 8-iso PGE(1), 8-iso PGE(2), 8-iso PGF(2alpha), 8-iso PGF(3alpha), and 8-iso-13,14-dihydro-15-keto PGF(2alpha) is antiaggregatory. Moreover, this inhibitory capacity is still apparent and may be enhanced in blood subjected to inflammatory stimulation. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 8 |
| Volume Number | 132 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2001-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Platelet Aggregation Drug Effects Prostaglandins, Synthetic Pharmacology 15-Hydroxy-11 Alpha,9 Alpha-(epoxymethano)prosta-5,13-dienoic Acid Collagen Enzyme Inhibitors In Vitro Techniques Inflammation Blood Lipopolysaccharides NG-Nitroarginine Methyl Ester Nitric Oxide Synthase Antagonists & Inhibitors Platelet Aggregation Inhibitors |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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