Disordered eicosanoid formation in pregnancy-induced hypertension.

P regnancy-induced hypertension is characterized by hypertension, proteinuria, edema, and, at times, abnormalities of the coagulation system and liver function. Reduced placental blood flow is a hallmark of the condition, and by definition, the blood pressure returns to normal after delivery. It occurs in 5 to 10% of all pregnancies, primarily in primigravidas after the 20th week of gestation. It occurs most frequently near term. Most cases are of moderate severity and respond to bed rest. The minority develop severe hypertension, which requires antihypertensive medication in addition to strict bed rest. The degree of severity is associated with changes in eicosanoid formation. This is best characterized in the cases of the vasoconstrictor and platelet agonist thromboxane A2 (TXA2) and the vasodilator and platelet inhibitor prostacyclin (PGI2). In normal pregnancy, there is an eightfold to 10-fold increase in PGI2 formation.1-3 In mild pregnancy-induced hypertension, this increase is less marked, approximately onefold to twofold. Alterations in the capacity of the placental and umbilical vasculature to synthesize prostacyclin have also been reported.4-8 Similarly, TXA2 biosynthesis also is enhanced in normal pregnancy. In severe pregnancy-induced hypertension, there is a marked elevation in TXA2 formation.9 It is possible that these alterations in eicosanoid formation occur as a result of an immunologically mediated vascular insult. Cardiac output increases by 30 to 40% in normal pregnancy.10,1' This change is evident by the 12th week of gestation and is the result of increases in heart rate and stroke volume. The increase in stroke volume is thought to be secondary to an increase in plasma volume that occurs in the first trimester and is sustained until term. Blood pressure falls during the first trimester, despite the increases in stroke volume and plasma volume, due to a fall in peripheral vascular resistance."'12 The reasons for the fall in peripheral vascular resistance have not been fully established but have been postulated to involve an increase in the synthesis of or response to vasodilator substances.13-'6 Pathophysiological features of pregnancy-induced hypertension include a reduction in placental blood flow, reversal of the normal circadian rhythm-resulting in