Epinephrine inhibits vascular hyperpermeability during platelet-activating factor- or ovalbumin-induced anaphylaxis

Platelet-activating factor (PAF) has been shown to play a critical role in mediating vascular hyperpermeability during anaphylaxis. Although epinephrine is the first-line treatment for anaphylaxis and can inhibit increased vascular permeability during anaphylaxis, the effect of epinephrine on PAF-induced vascular hyperpermeability is still unclear. In this study, we investigated whether epinephrine can reduce vascular permeability and alleviate anaphylactic symptoms induced by PAF. We tested vascular permeability in vivo by measuring the Evans blue dye leakage and in vitro by transendothelial electrical resistance measurement. Blood pressure was measured with a noninvasive monitoring system. Body temperature was recorded using an electronic thermometer. Confocal microscopy was used to characterize gap areas of human umbilical vein endothelial cells (HUVECs). Phosphorylation of VE-cadherin was assessed using western blot. (1) We observed that epinephrine substantially inhibited PAF-induced vascular permeability in vivo and in vitro. In vivo, administration of epinephrine significantly decreased PAF-induced Evans blue leakage and ear swelling, elevated hematocrit levels and maintained sufficient blood supply to the brain. In vitro, administration of epinephrine alleviated PAF-induced gap numbers and areas in HUVECs. (2) We found that epinephrine can inhibit PAF or ovalbumin (OVA)-induced anaphylactic symptoms. Epinephrine administration effectively inhibited hypothermia and hypotension induced by PAF or OVA. Timely epinephrine administration dramatically decreased the PAF-induced mortality rate. (3) We found that epinephrine inhibited the release of PAF during OVA-induced anaphylaxis. In conclusion, epinephrine administration can reduce PAF-induced vascular hyperpermeability and anaphylactic symptoms, including hypothermia and hypotension. Early addition of epinephrine was critical for the control of PAF-induced anaphylaxis.