Involvement of prostaglandin F in preeclamptic human umbilical vein vasospasm: a role of prostaglandin F and thromboxane A2 receptors


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Abstract

ObjectivePreeclampsia is characterized by hypertension and proteinuria developing after 20 weeks of gestation. Increased vasoconstriction can be one of the major underlying pathophysiological event in this syndrome. We examined the role of vasoconstrictor prostanoid, prostaglandin F (PGF) in preeclamptic and normotensive human umbilical veins.MethodsUmbilical veins were set up in organ bath. The concentration-response curves of PGF (endogenous agonist of prostaglandin F receptor) and fluprostenol (prostaglandin F receptor selective agonist) were determined in normal and preeclamptic veins either in the absence or presence of BAY u3405 (thromboxane A2 receptor selective antagonist). PGF and its major metabolite concentrations were measured by enzyme immunoassay kit. The expression of vasoconstrictor prostanoid receptors was determined by western blot.ResultsThe concentration-dependent contractions to PGF and fluprostenol were significantly increased in umbilical vein preparations derived from preeclamptic women compared with those of normotensives. Increased reactivity was related with enhanced sensitivity to these spasmogens in preeclamptic veins. BAY u3405 (10 μmol/l) did not modify the responsiveness to PGF in normal umbilical veins whereas moderately reduced the contractions in preeclamptic preparations. Serum concentrations of PGF and its major metabolite, 13,14-dihydro-15-keto-PGF2α, were comparable between preeclamptics and normotensives whereas the metabolite concentration was elevated in umbilical cord serum of preeclamptics. 13,14-dihydro-15-keto-PGF2α, release was also increased in umbilical vein preparations of preeclamptic women. An increased prostaglandin F receptor protein expression was determined whereas EP3 and thromboxane A2 protein expressions were unchanged in preeclamptic umbilical veins.ConclusionProstaglandin F and thromboxane A2 receptors activation by PGF could be involved in umbilical vasospasm observed in preeclampsia.

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