Role of thromboxanes and prostaglandin endoperoxides in the pathogenesis of eicosanoid induced sudden death.
Arachidonic acid (1 mg/kg) or 9,11-azo PGH2 (35 micrograms/kg) injected intravenously into anesthetized rabbits results in sudden death characterized by a marked loss of circulating platelets, a dramatic rise in circulating thromboxane B2 concentrations and a precipitous drop in blood pressure. Death ensues in 3 to 5 minutes from pulmonary thrombosis and pulmonary artery constriction. Administration of dazoxiben (2 mg/kg) prior to arachidonic acid, prevents all of these changes. However, dazoxiben failed to prevent any of these effects after injection of azo-PGH2, a synthetic agonist of the endoperoxide and thromboxane receptor. These results demonstrate the importance of endoperoxide-thromboxane accumulation in eicosanoid induced sudden death and suggests that there is no significant functional difference between the actions of these agents in the rabbit.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D003645:Death, Sudden / Q000209:etiology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation; D011449:Prostaglandin Endoperoxides / Q000502:physiology*; D011463:Prostaglandins H / Q000494:pharmacology; D011655:Pulmonary Embolism / Q000209:etiology*; D011817:Rabbits; D013928:Thromboxane A2 / Q000502:physiology*; D013931:Thromboxanes / Q000502:physiology*; D014661:Vasoconstriction
D001095:Arachidonic Acids; D007093:Imidazoles; D011449:Prostaglandin Endoperoxides; D011463:Prostaglandins H; D013931:Thromboxanes; C029166:dazoxiben; D016718:Arachidonic Acid; D013928:Thromboxane A2; C013824:azo analog II