EFFECTS OF HYDROXYETHYLRUTOSIDES ON HYPOXIA-INDUCED ACTIVATION OF HUMAN ENDOTHELIAL-CELLS IN-VITRO

1 A clinically available mixture of hydroxyethylrutosides (HR) was exa mined as inhibitors of endothelial cell activation by hypoxia in vitro . Thus, the effects of HR on ATP depletion, phospholipase A(2) activat ion and neutrophil adherence were investigated in hypoxia-activated hu man umbilical vein endothelial cells in primary cell culture. 2 Our re sults show that HR inhibited two important steps of the activation of endothelial cells by hypoxia: the decrease in ATP content, which is th e starting point of the process, and the activation of phospholipase A (2) one enzyme responsible for the release of inflammatory mediators. This inhibition was dose-dependent with 70 to 90% inhibition at 500 mu gml(-1) of HR. 3 In addition, hypoxia-activated endothelial cells inc reased their adhesiveness for neutrophils. This process could also be prevented in a dose-dependent manner if endothelial cells were incubat ed in the presence of HR. This inhibition was confirmed by a morpholog ical study. 4 In conclusion, the results of this study suggest that a possible explanation for the improvement in venous insufficiency by HR observed clinically could be their ability to inhibit the activation of endothelial cells during blood stasis.