title: Dual inhibition of thromboxane A2 synthesis and thromboxane A2/prostaglandin endoperoxide receptors by ridogrel: anti-thrombotic effect in vivo in rat mesenteric arteries.
abstract: In rats treated with acetylsalicylic acid (100 mg/kg i.v., -3 h) to block platelet cyclo-oxygenase, a superfusion with tranylcypromine (TCP, 3 x 10(-3) M) plus arachidonic acid (AA; 1 x 10(-4) M) significantly enhances (+70%) the opto-electronically monitored formation of a thrombus, elicited by a superfusion with ADP (4 x 10(-4) M for 45 s) over a de-endothelialized site of a mesenteric artery (200-300 microns diameter). Treatment with ridogrel at doses blocking either singly thromboxane A2 (TxA2) synthetase (0.63 mg/kg i.v., -15 min, n = 6) or additionally TxA2/prostaglandin endoperoxide receptors (5 mg/kg i.v., -15 min, n = 6) reduces (-74%) or abolishes (-100%) respectively the enhancement by TCP + AA of the ADP-induced thrombus formation. These observations demonstrate (1) a transfer of prostaglandin endoperoxides from the vessel wall to the platelets to reinforce thrombus formation in vivo; (2) the antithrombotic potential of combined TxA2 synthetase inhibition plus TxA2/prostaglandin endoperoxide receptor blockade with ridogrel.
authors.affiliation: Laboratory of Physiology and Physiopathology, Faculty of Medicine, V.U.B., Belgium.
authors.forename: R H
authors.initials: RH
authors.lastname: Bourgain
authors.forename: R
authors.initials: R
authors.lastname: Andries
authors.forename: K
authors.initials: K
authors.lastname: Decuyper
authors.forename: F
authors.initials: F
authors.lastname: De Clerck
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D010421:Pentanoic Acids / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane; D013927:Thrombosis / Q000139:chemically induced; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014191:Tranylcypromine / Q000494:pharmacology
chemical_list: D005343:Fibrinolytic Agents; D010421:Pentanoic Acids; D011725:Pyridines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C055662:prostaglandin endoperoxide receptor; D016718:Arachidonic Acid; D014191:Tranylcypromine; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; C060219:ridogrel