Characterization of the effects of isoprostanes on platelet aggregation in human whole blood
Open Access
- 1 April 2001
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 132 (8), 1699-1706
- https://doi.org/10.1038/sj.bjp.0704019
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.Keywords
This publication has 65 references indexed in Scilit:
- Vasoconstrictor Effects of Iso-Prostaglandin F2α Type-III (8-Iso-Prostaglandin F2α) on Human Saphenous VeinsJournal of Cardiovascular Pharmacology, 2000
- Vascular effects of isoprostanes after endothelial damageProstaglandins, Leukotrienes & Essential Fatty Acids, 1999
- Phosphorylation of the Thromboxane Receptor α, the Predominant Isoform Expressed in Human PlateletsPublished by Elsevier BV ,1999
- The F 2 -Isoprostane 8-Epiprostaglandin F 2α Increases Platelet Adhesion and Reduces the Antiadhesive and Antiaggregatory Effects of NOArteriosclerosis, Thrombosis, and Vascular Biology, 1998
- 8-ISO-PGF2α PRODUCTION BY ALVEOLAR MACROPHAGES EXPOSED TO HYPEROXIAShock, 1998
- Increased Circulating Products of Lipid Peroxidation in Patients with Alcoholic Liver DiseaseAlcohol: Clinical and Experimental Research, 1998
- Release of Isoprostanes by Human Pulmonary Artery in Organ Culture: A Cyclo-oxygenase and Nitric Oxide Dependent PathwayBiochemical and Biophysical Research Communications, 1997
- Modulatory effect of 8-iso-PGE2 on plateletsGeneral Pharmacology: The Vascular System, 1997
- Platelet prostanoid receptorsPharmacology & Therapeutics, 1996
- Vascular Smooth Muscle Actions and Receptor Interactions of 8-Iso-prostaglandin E2, an E2-IsoprostaneBiochemical and Biophysical Research Communications, 1993