DISTINCT FACTORS IN PLASMA OF PREECLAMPTIC WOMEN INCREASE ENDOTHELIALNITRIC-OXIDE OR PROSTACYCLIN

The pathogenesis of preeclampsia is proposed to be due to uncharacteri zed circulating factors that activate endothelial cells. Support for t his hypothesis is provided by in vitro activation of endothelial cells by plasma from preeclamptic women, eg, increased nitric oxide and pro stacyclin generation. We performed molecular sizing, lipid extraction, and Lipoprotein fractionation of plasma from normal pregnant and pree clamptic women and determined the ability of these plasma fractions to increase nitric oxide or prostacyclin generation by endothelial cells . Fractions from plasma of preeclamptic women were consistently more a ctive than fractions from normal pregnant women, although characteriza tion was qualitatively similar. The factors stimulating nitric oxide a nd prostacyclin were different. The factor (or factors) stimulating ni tric oxide generation was extractable by charcoal and present in lipid extracts and lipoprotein isolates with a molecular weight greater tha t 1.5 million daltons, which is characteristic of a lipoprotein or lip oprotein aggregate. By contrast,activity to stimulate prostacyclin per sisted after charcoal stripping or lipoprotein removal, partitioned to the aqueous fraction,ld had a molecular weight of approximately 50 00 0 D. Two distinct factors in the blood of preeclamptic women alter end othelial function in vitro. This information should guide the search f or circulating factors contributing to the pathophysiology of preeclam psia.