Pregnancy and lipid peroxide-induced alterations of eicosanoid-metabolizing enzymes in the aorta of the rat

Abstract

We examined whether pregnancy modulates the expression of prostaglandin endoperoxide synthase, prostacyclin synthase, and thromboxane A2 synthase in the systemic vasculature. Further, we examined whether elevated lipid peroxidation during pregnancy (induced by vitamin E deprivation) affects the normal adaptive process to pregnancy. Western immunoblotting was performed on aortas from normal and vitamin E-deprived late pregnant (18 to 19 days) and age-matched virgin control rats. Normal pregnancy resulted in an increased expression of prostaglandin endoperoxide synthase (2.91 vs 1.06 fmol/ng deoxyribonucleic acid, p < 0.05). Surprisingly, the expression for both prostacyclin and thromboxane A2 synthases were significantly decreased by pregnancy: prostacyclin synthase 2.60 versus 13.82 units/ng deoxyribonucleic acid and thromboxane A2 synthase 1.32 versus 9.85 units/ng of deoxyribonucleic acid. Elevation of endogenous lipid peroxidation partially reversed this normal pregnancy trend in enzyme expression: prostaglandin endoperoxide synthase 1.85 fmol/ng deoxyribonucleic acid, prostacyclin synthase 9.38 units/ng deoxyribonucleic acid, thromboxane A2 synthase 4.36 units/ng deoxyribonucleic acid. Changes in prostanoid activity in the systemic vasculature during pregnancy may be mediated by concerted induction and down-regulation of specific enzymes. Increased lipid peroxidation interferes with this normal pregnant pattern. Further studies on the cell-specific expression of these genes will help to define the cardiovascular role of prostaglandins in pregnancy and in preeclampsia.