Protective actions of a new thromboxane synthetase inhibitor in arachidonate induced sudden death.
A new thromboxane synthetase inhibitor, OKY-046, at doses of 0.5 and 1.0 mg/kg prevented mortality induced by sodium arachidonate in 100% of the rabbits studied. Sodium arachidonate at a dose of 1.25 mg/kg uniformly decreased mean arterial blood pressure to values approximately 0 mm Hg, stopped respiration and produced sudden death within 3-5 minutes in all rabbits studied. OKY-046 prevented all these sequelae of the sodium arachidonate. Untreated rabbits challenged with sodium arachidonate develop large increases in circulating thromboxane B2 (TxB2) and 6-keto PGF1 alpha of about 12- to 18-fold. In contrast, OKY-046 prevented the increase in TxB2 concentrations and the pulmonary thrombosis, but did not block the rise in 6-keto PGF1 alpha following arachidonate injection. These results suggest that the protective mechanism of OKY-046 in arachidonate induced sudden death is via selective inhibition of thromboxane synthesis.
D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects; D008689:Methacrylates / Q000494:pharmacology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D012119:Respiration / Q000187:drug effects; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects
D000179:Acrylates; D001095:Arachidonic Acids; D008689:Methacrylates; D016718:Arachidonic Acid; D013929:Thromboxane B2; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; C034364:ozagrel