Antagonism by antipyretics of the hyperthermic effect of a prostaglandin precursor, sodium arachidonate, in the cat.
1. Injection of sodium arachidonate (100-400 mug) into lateral cerebral ventricles of unanaesthetized cats caused shivering and rapid development of dose-related hyperthermic responses. Unless arachidonate is hyperthermogenic per se, this indicates that in vivo formation of prostaglandins, or perhaps an endoperoxide intermediate, can cause hyperthermia. 2. Tolerance gradually developed when arachidonate was administered repeatedly at intervals of 1-7 days. Examination of the brains of several tolerant animals revealed in each case marked enlargement of the lateral ventricles which apparently accounted for the diminished response to arachidonate. 3. Sodium salicylate (40, 160 mg/kg, i.v.) antagonized arachidonate but only after a 3-4 hr latent period. 4. Paracetamol (10, 40 mg/kg, i.v.) reduced the hyperthermic effect of arachidonate but a dose of 40 mg/kg antagonized centrally administered bacterial endotoxin more effectively than it did arachidonate. 5. Indomethacin (40 mug/kg, i.v.) significantly reduced arachidonate-induced hyperthermia in only one of two studies. This reduction was comparable to the hypothermic effect of indomethacin in afebrile animals and was attributed to a non-specific action on thermoregulatory function rather than to inhibition of prostaglandin synthesis. Indomethacin antagonized endotoxin and leucocytic pyrogen to a greater degree than it did arachidonate. 6. Comparison of the relative effectiveness of the antipyretics in blocking hyperthermic responses to pyrogens and to sodium arachidonate indicates that, if prostaglandins do mediate pyrogen-induced fever, these antipyretics exert their primary at a step before prostaglandin synthesis.
D000082:Acetaminophen / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors*; D001831:Body Temperature / Q000187:drug effects*; D002415:Cats; D005334:Fever / Q000139:chemically induced; D007213:Indomethacin / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D012459:Salicylates / Q000494:pharmacology
D000700:Analgesics; D001095:Arachidonic Acids; D011453:Prostaglandins; D012459:Salicylates; D000082:Acetaminophen; D007213:Indomethacin