Effect of epinephrine on platelet-activating factor–stimulated human vascular smooth muscle cells

BackgroundAnimal and human data show that platelet-activating factor (PAF) mediates the life-threatening manifestations of anaphylaxis. Although administration of epinephrine is the mainstay of therapy of acute anaphylaxis, the interaction between epinephrine and PAF has not been studied. In particular, the effect of the timing of epinephrine administration on the action of PAF has not been examined.ObjectiveUsing human vascular smooth muscle cells (HVSMCs), we examined the effect of timing of epinephrine addition on the action of PAF.MethodsThe effect of epinephrine on PAF-mediated prostaglandin E2 (PGE2) release from human aortic smooth muscle cells was examined. Epinephrine was added at various times before and after PAF stimulation.ResultsHVSMCs stimulated with PAF released PGE2 in a concentration- and time-dependent manner. Whereas preincubation of HVSMCs with epinephrine before the addition of PAF suppressed PGE2 release, treatment with epinephrine after PAF stimulation was less effective with time after PAF stimulation. PGE2 release was suppressed by means of preincubation with 8-bromo–cyclic AMP and forskolin.ConclusionsPAF induced PGE2 release from HVSMCs in a concentration- and time-dependent manner, and early addition of epinephrine was essential for the control of PAF-induced PGE2 release. Epinephrine was most effective when administered before stimulation with PAF but was progressively less effective with time after PAF stimulation.