Eicosanoids in Preeclampsia-Eclampsia: The Effects of Magnesium

Abstract

Magnesium sulfate is the cornerstone of therapy for the management of eclampsia and has been for the better part of a century (1, 2). Magnesium reduces reactivity of blood vessels, including those of the cerebral circulation, and inhibits platelet aggregation (3, 4). These properties of magnesium may directly contribute to reversal of the underlying pathogenesis of eclampsia. There is evidence that some of the beneficial effects of magnesium are related to promotion of the synthesis of vasodilator prostaglandins, of which one, prostacyclin (PGI₂), also inhibits platelet aggregation (5, 6) (Fig. 1). Preeclampsia and eclampsia have been proposed to represent a state of relative prostaglandin deficiency, or more precisely, when considered in terms of platelet abnormalities, one of insufficient PGI₂ production by blood vessels, especially those of the placenta (7). As vascular prostacyclin inhibits platelet synthesis of thromboxane A₂ (TxA₂), the two principal actions of TxA₂, promotion of platelet aggregation and vasoconstriction, will go unchecked in the face of insufficient PGI₂ production by blood vessels (8, 9). In contrast, normal pregnancy has been characterized as a state of enhanced prostaglandin production in which prostacyclin and PGE₂ levels are elevated in the fetal and maternal circulations (10, 11). The endothelial lining of the vasculature can be conceptualized as an organ which generates prostacyclin and other mediators that affect platelet function, cell growth, and vasomotion. The blood vessels of the uteroplacental complex, as well as the systemic vasculature, during the progression of normal pregnancy generate increasing quantities of prostaglandins, a function that may underlie the diminished vasoconstrictor responses and pressor effects of angiotensin II (AII) (12) as both PGI₂ and PGE₂ antagonize the circulatory actions of All as well as those of other pressor hormones (13, 14). In addition to a decline in the synthesis of PGI2 that heralds the onset of preeclampsia, there is diminished production of PGE₂, the prototypical modulator prostaglandin that inhibits the vasoconstrictor and salt- and water-retaining actions of pressor hormones including AII (14,15). Whether the inhibitory effects of magnesium on vascular reactivity and platelet activation are related to a common factor, such as promotion of prostacyclin formation in preeclampsia and eclampsia (4, 16), cannot be answered unequivocally although there is evidence that magnesium augments prostaglandin-dependent vascular mechanisms associated with inhibition of platelet activation.