Protective effects of a new specific thromboxane antagonist in arachidonate-induced sudden death.
Sodium arachidonate (NaAr), at a dose of 2.0 mg/kg injected i.v., is uniformly lethal in rabbits within 5 min. This sudden death is typified by a precipitous drop in mean arterial blood pressure, a dramatic decrease in the circulating platelet count, and by a sharp rise in plasma thromboxane A2 (TxA2) concentration. Pretreatment with BM-13,505, a novel thromboxane receptor antagonist, at doses ranging from 0.25 mg/kg to 2.0 mg/kg resulted in 100% survival of rabbits subjected to sodium arachidonate injection. BM-13,505 pretreatment also inhibited the decreases in circulating platelet count and in blood pressure associated with arachidonic acid injection. BM-13,505 did not inhibit the sharp rise in plasma TxB2 concentrations at any dose. This evidence suggests that the mechanism of BM-13,505 protection is by means of thromboxane receptor antagonism and not via inhibition of thromboxane A2 synthesis.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D003645:Death, Sudden / Q000209:etiology*; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology*; D010976:Platelet Count / Q000187:drug effects; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D001095:Arachidonic Acids; D010648:Phenylacetates; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013931:Thromboxanes; D016718:Arachidonic Acid; D013929:Thromboxane B2; C051762:daltroban