Endothelium-derived prostacyclin: effect of serum from women with normal and hypertensive pregnancy

Abstract

1. Pregnancy-induced hypertension (or pre-eclampsia) is characterized by vasoconstriction, platelet aggregation and altered capillary permeability, implying disordered endothelial function and/or structure. Serum from women with pregnancy-induced hypertension has been reported by others to be cytotoxic to endothelial cells in vitro. We hypothesized that such serum contains a factor that limits the ability of endothelial cells to produce and/ or release prostacyclin. 2. Prostacyclin production by intact and damaged cultured human umbilical vein endothelial cells was measured after incubating these cells with serum from non-pregnant and normal pregnant women and women with pregnancy-induced hypertension. Confluent human umbilical vein endothelial cell monolayers (intact and damaged) were incubated with sera for 24 h at 37°C followed by 1 h of incubation with added thrombin (stimulated production) or media (basal production). Supernatants were then collected for measurement of 6-keto-prostaglandin F1α by radioimmunoassay. 3. Basal production of 6-keto-prostaglandin F1α was greater in response to serum from non-pregnant women than to that from pregnant women. Within each group, sub-lethally damaged cells had a similar basal production of 6-keto-prostaglandin F1α to that of intact cells. 4. Basal production of 6-keto-prostaglandin F1α by intact or damaged cells incubated with sera from normal pregnant women and from women with pregnancy-induced hypertension was similar. 5. In all groups the addition of thrombin to intact endothelial cells increased 6-keto-prostaglandin F1α production approximately 15–30-fold over basal levels, but only three- to five-fold in damaged endothelial cells. Stimulated production of 6-keto-prostaglandin F1α by intact or damaged cells was similar with sera from normal pregnant women and women with pregnancy-induced hypertension. 6. These results indicate that any cytotoxic factor present in the sera of women with pregnancy-induced hypertension is unlikely to act by reducing basal endothelial production of prostacyclin. Secondly, if endothelial cell injury occurs in these women they may have a reduced capacity to increase endothelial production of prostacyclin in response to thrombin and possibly other important physiological stimuli.