PLASMA OF PREECLAMPTIC WOMEN STIMULATES AND THEN INHIBITS ENDOTHELIALPROSTACYCLIN

We propose that the dichotomy between the in vivo reduction in intrava scular prostacyclin production that occurs in preeclampsia and the in vitro stimulatory effect of plasma from preeclamptic patients on endot helial cell prostacyclin production is due to differential effects of chronic versus acute exposure to the plasma. We studied the acute vers us chronic effects of 2% plasma from healthy pregnant and preeclamptic subjects by measuring endothelial prostacyclin production at differen t time periods after exposure to plasma. To determine whether such eff ects sere specific to prostacyclin, we also measured prostaglandin E(2 ) production. To determine whether chronic changes in prostacyclin pro duction resulted from altered cellular responsiveness, we stimulated c ells that had been exposed to plasma for 72 hours with arachidonic aci d and measured prostaglandin production. Preliminary characterization of the plasma factor or factors responsible for alterations in prostag landin production was performed. After 24 hours cells exposed to plasm a from preeclamptic women produced more prostacyclin and prostaglandin E(2) than cells exposed to plasma from healthy pregnant women. In con trast, after 72 hours exposure to plasma from preeclamptic women resul ted in less endothelial cell prostacyclin production than exposure to plasma from healthy pregnant women, but there were no such differences in prostaglandin E(2) production. Cells that had been exposed to plas ma from preeclamptic women for 72 hours produced less prostacyclin but the same quantity of prostaglandin E(2) after stimulation with arachi donic acid than cells exposed to plasma from healthy pregnant women. T he plasma factor or factors responsible for altered prostacyclin produ ction were sensitive to heat, acid, and proteases. In contrast to acut e exposure, chronic exposure to plasma from preeclamptic women alters endothelial cells to result in decreased prostacyclin production, an o bservation consistent with in vivo findings.