Platelet-activating factor antagonists in experimental shock

Platelet-activating factor (PAF) at 10 micrograms/kg i.v. induced profound hyperkalemia, changes of hematological parameters, patterns of ECG, and acid-base balance in rats. In separate experiments infusions of PAF at 30 ng/kg/min or injection of endotoxin from E. coli (15 mg/kg i.v.) induced a marked drop in blood pressure. All these changes were antagonized by pretreatment or post-treatment (in case of hypotension) by the selective hetrazepinoic PAF antagonists apafant (WEB 2086, CAS 105219-56-5; 0.1-5 mg/kg i.v.), bepafant (WEB 2170, CAS 114776-28-2; 0.05-1.0 mg/kg i.v.), or STY 2108 (0.01-0.1 mg/kg), respectively. The results support the view that PAF can mimic features of endotoxin shock and that the hetrazepines (like apafant, bepafant) are useful tools to clarify the role of PAF in such conditions.