PLATELET-ACTIVATING-FACTOR IMPAIRS PRESSER RESPONSES TO NORADRENALINEIN THE ANESTHETIZED RAT BUT DOES NOT MEDIATE ENDOTOXIN-INDUCED HYPOREACTIVITY

A nonhypotensive dose of endotoxin (Escherichia coli lipopolysaccharid e, 250 mu g kg(-1) h(-1)) impaired both the presser responsiveness to noradrenaline and its effects in reducing renal and hindquarter blood flow, measured using ultrasound Doppler flow probes. Platelet activati ng factor (PAF, 50 ng kg(-1) h(-1)) similarly impaired presser respons iveness to noradrenaline, although this effect was accompanied by mark ed hypotension. These actions of PAF were prevented by pretreatment wi th 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 i n mediating endotoxin-induced vascular hyporeactivity, at least in the early stages of endotoxaemia. (C) 1994 Wiley-Liss, Inc.