Neutrophil Platelet-Activating Factor in Normal and Hypertensive Pregnancy and in Pregnancy-Induced Hypertension

Abstract

1. Platelet-activating factor is a phospholipid with potent vasodilator and platelet-activating properties. To test the hypothesis that a generalized change in cellular platelet-activating factor metabolism may be involved in the systemic vasodilatation of normal pregnancy or pregnancy-induced hypertension, we studied platelet-activating factor and eicosanoid synthesis in isolated leucocytes obtained from pregnant women before and after delivery compared with age-matched non-pregnant control subjects. Parallel observations were carried out in age- and gestation-matched women with uncomplicated hypertension in pregnancy and in women with pregnancy-induced hypertension and a further set of normotensive pregnant control subjects. 2. Leucocyte counts were higher in all pregnant groups compared with non-pregnant control subjects. Neutrophil production of platelet-activating factor and metabolites of prostacyclin, prostaglandin E2 and thromboxane in response to calcium ionophore stimulation were all lower in pregnant women compared with non-pregnant control subjects, but returned to similar levels 6 weeks post partum. There was no significant difference between essential hypertensive and normotensive groups. When women with pregnancy-induced hypertension were a priori subdivided into those with or without proteinuria, subjects with proteinuria showed significantly lower levels of neutrophil platelet-activating factor synthesis. 3. Plasma levels of the platelet-activating factor metabolite (lyso-platelet-activating factor) were also lower in pregnancy, suggesting alterations in the activity of enzymes controlling synthesis or degradation of this phospholipid in pregnancy. In pregnancy-induced hypertension the levels of plasma lyso-platelet-activating factor were higher than in normal pregnancy. 4. Thus this study demonstrates a reduction in the maximum capacity of neutrophils to synthesize platelet-activating factor and the three main classes of eicosanoids in vitro and a reduction in plasma lyso-platelet-activating factor levels in normotensive and essential hypertensive pregnancies. Contrary to expectation neutrophil prostacyclin metabolite generation was reduced in normal pregnancy. In pregnancy-induced hypertension with proteinuria the suppression of neutrophil platelet-activating factor synthesis was more pronounced. The results do not support the involvement of platelet-activating factor in the vasodilatation of pregnancy, but indicate profound changes in cellular phospholipid metabolism in normal pregnancy with further disturbances in pregnancy-induced hypertension by as yet unexplained mechanisms.