PLATELET ACTIVATING FACTOR (PAF) INVOLVEMENT IN ENDOTOXIN-INDUCED HYPOTENSION IN RATS - STUDIES WITH PAF-RECEPTOR ANTAGONIST KADSURENONE

Evidence from 3 types of experiments indicates that platelet activating factor (PAF) is an important mediator of endotoxin-induced hypotension in rats. Endotoxin infusion stimulates the time-dependent appearance of PAF in the blood. PAF infusion results immediately (< 30 s) in hypotension while endotoxin-induced hypotension takes 3-5 min to occur, allowing time for PAF production. Infusion of the specific PAF-receptor antagonist kadsurenone (2.2 .mu.mol/kg bolus, 0.9 .mu.mol/min/kg continuous infusion), which inhibits PAF-induced hypotension by 67%, causes a 67% reversal of endotoxin-elicited hypotension. Rats respond hypotensively to each of a series of low-dose PAF infusions but only to the 1st low-dose endotoxin infusion. These endotoxin-refractory rats do respond to subsequent PAF infusions.