Is platelet activating factor (PAF) a mediator of endotoxin shock?
To determine whether endogenous PAF contributes to the pathogenesis of endotoxin shock, CV-3988, a specific PAF antagonist, was injected i.v. to rats before, simultaneously with or after endotoxin. CV-3988 (5 mg/kg i.v.) injected 5 min before the endotoxin completely inhibited endotoxin (15 mg/kg i.v.)-induced hypotension, and CV-3988 (0.05-1 mg/kg i.v.) injected 7-10 min after the endotoxin rapidly reversed endotoxin-induced hypotension. A combination of CV-3988 (10 mg/kg) with endotoxin (5 mg/kg) administered i.v. improved the survival rate for 20 h or more. CV-3988 (0.05-1 mg/kg i.v.) rapidly reversed the PAF (1 microgram/kg i.v.)-induced hypotension. These findings strongly suggest that endogenous PAF may play a pivotal role in the pathogenesis of endotoxin shock.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity; D008297:Male; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000503:physiopathology*; D013844:Thiazoles / Q000494:pharmacology
D004731:Endotoxins; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D013844:Thiazoles; C037913:CV 3988