Renal prostacyclin and thromboxane in normotensive and preeclamptic pregnant women and their infants.
Renal synthesis of the antiaggregatory and vasodilatory prostacyclin and its endogenous antagonist thromboxane A2 may be disturbed in patients with preeclampsia. We tested this hypothesis by measuring 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha; a hydration product of prostacyclin), 2,3-dinor-6-keto-PGF1 alpha (generated from 6-keto-PGF1 alpha through beta-oxidation) and thromboxane B2 (a hydration product of thromboxane A2) in the urine of healthy pregnant and preeclamptic women. Urinary excretion of 6-keto-PGF1 alpha [19.8 +/- 10.5 pmol/mmol creatinine, (mean +/- SD)] and 2,3-dinor-6-keto-PGF1 alpha (19.2 +/- 7.5 pmol/mmol creatinine) increased during normal pregnancy, reaching a maximum (about 5-fold rise) during the last month of pregnancy. No significant changes occurred in the urinary excretion of thromboxane B2. In women with severe preeclampsia (n = 17), the excretion of both 6-keto-PGF1 alpha (37.7 +/- 29.5 pmol/mmol creatinine) and 2,3-dinor-6-keto-PGF1 alpha (54.5 +/- 56.2 pmol/mmol creatinine) was lower (P less than 0.001) than in the normotensive women during the last trimester of pregnancy (80.6 +/- 43.7 and 98.7 +/- 42.9 pmol/mmol creatinine, respectively). The neonates excreted 6-25 times more 6-keto-PGF1 alpha, 2,3-dinor-6-keto-PGF1 alpha and thromboxane B2 than did the nonpregnant women. In contrast to the adults, neonatal 6-keto-PGF1 alpha excretion was 2-3 times greater than that of 2,3-dinor-6-keto-PGF1 alpha suggesting reduced beta-oxidation in the newborns. Infants born to preeclamptic women had reduced output of 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha on the first day of life. Thus, renal prostacyclin synthesis is diminished in women with severe preeclampsia and their infants.
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D049590:Postpartum Period / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000652:urine
D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D011464:Epoprostenol