The effect of arachidonic acid metabolism on intravascular platelet aggregation in rats.
The effects of BW755C, benoxaprofen, indomethacin and piroxicam were studied on intravascular platelet aggregation using continuous platelet counting. Plasma levels of thromboxane B2 (TxB2) and 6-keto prostaglandin F1 (6-keto PGF1 alpha) were measured by radioimmunoassay. BW755C, a dual inhibitor of arachidonic acid metabolism, potentiated or inhibited aggregation depending on dose. BW755C increased TxB2 and 6-keto PGF1 alpha plasma levels at low doses. At higher doses BW755C inhibited aggregation and reduced TxB2 plasma levels. At 16 mg/kg BW755C, 6-keto PGF1 alpha was detected. Benoxaprofen also potentiated collagen-induced aggregation. 8 mg/kg indomethacin was shown to have a short lasting increased inhibitory action on collagen-induced aggregation when compared with the more specific cyclooxygenase inhibitor, piroxicam. 6-keto PGF1 alpha was detected in plasma from rats treated with indomethacin and piroxicam. The results obtained using low doses of BW755C suggest that the lipoxygenase pathway is involved in platelet aggregation. Interpretation of the results obtained using higher doses of drugs also suggests this involvement though some nonspecific actions of the drugs must be taken into consideration. Further work is required to detail the role of lipoxygenase products in collagen-induced intravascular platelet aggregation.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D003094:Collagen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D010894:Piroxicam; D010974:Platelet Aggregation / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D013843:Thiazines / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D011422:Propionates; D011720:Pyrazoles; D013843:Thiazines; D010894:Piroxicam; C011677:benoxaprofen; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D003094:Collagen; D007213:Indomethacin