Platelet activating factor impairs pressor responses to noradrenaline in the anaesthetized rat but does not mediate endotoxin-induced hyporeactivity.

Abstract

A nonhypotensive dose of endotoxin (Escherichia coli lipopolysaccharide, 250 micrograms kg-1 h-1) impaired both the pressor responsiveness to noradrenaline and its effects in reducing renal and hindquarter blood flow, measured using ultrasound Doppler flow probes. Platelet activating factor (PAF, 50 ng kg-1 h-1) similarly impaired pressor responsiveness to noradrenaline, although this effect was accompanied by marked hypotension. These actions of PAF were prevented by pretreatment with the PAF antagonists WEB 2086 (20 mg kg-1) or BN 50739 (10 mg kg-1) 15 min before commencing the infusion. However, neither antagonist modified the effect of endotoxin in impairing vascular responsiveness to noradrenaline. Thus, these results do not support a role for PAF in mediating endotoxin-induced vascular hyporeactivity, at least in the early stages of endotoxaemia.