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

Background: Animal 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. Objective: Using human vascular smooth muscle cells (HVSMCs), we examined the effect of timing of epinephrine addition on the action of PAF. Methods: The effect of epinephrine on PAF-mediated prostaglandin E-2 (PGE(2)) release from human aortic smooth muscle cells was examined. Epinephrine was added at various times before and after PAF stimulation. Results: HVSMCs stimulated with PAF released PGE(2) in a concentration-and time-dependent manner. Whereas preincubation of HVSMCs with epinephrine before the addition of PAF suppressed PGE(2) release, treatment with epinephrine after PAF stimulation was less effective with time after PAF stimulation. PGE(2) release was suppressed by means of preincubation with 8-bromo-cyclic AMP and forskolin. Conclusions: PAF induced PGE(2) release from HVSMCs in a concentration-and time-dependent manner, and early addition of epinephrine was essential for the control of PAF-induced PGE(2) release. Epinephrine was most effective when administered before stimulation with PAF but was progressively less effective with time after PAF stimulation. (J Allergy Clin Immunol 2012;129:1329-33.)