Prostacyclin, thromboxane A and the effect of low-dose ASA in pregnancies at high risk for hypertensive disorders.
BACKGROUND
The aim of this study was to investigate the prostanoid production in pregnancies at high risk for hypertensive disorders, and the effect of low-dose acetylsalicylic acid (ASA) on prostanoids.


METHODS
Ninety women with a bilateral notching in uterine arteries screened by Doppler ultrasound at 12-14 gestational weeks were randomized to the ASA (0.5 mg/kg/day) or placebo group. Forty-three women in both groups were followed up throughout the pregnancy. Urine samples were taken at baseline, and at 24-26 and 32-34 weeks of gestation to determine the urinary 11-dehydrothromboxane B(2) (u-11-dehydro-TxB(2)) and 2,3-dinor-6-keto-prostaglandin F(1alpha) (u-2,3-dinor-6-keto-PGF(1alpha)), the metabolites of thromboxane A(2) and prostacyclin, respectively.


RESULTS
In the pregnancies with pregnancy-induced hypertension (PIH) before 37 gestational weeks, the 2,3-dinor-6-keto-PGF(1alpha)/11-dehydro-TxB(2) ratio did not increase as much as in other pregnancies (P = 0.028). In the placebo group pregnancies with preeclampsia had significantly lower 2,3-dinor-6-keto-PGF(1alpha) (P = 0.019) at 12-14 weeks of gestation compared to other pregnancies. In the placebo group the 2,3-dinor-6-keto-PGF(1alpha)/11-dehydroTxB(2) ratio remained unchanged throughout the pregnancy, with no significant difference between pregnancies with a normal or an adverse outcome. In the ASA group the 2,3-dinor-6-keto-PGF(1alpha)/11-dehydro-TxB(2) ratio increased (P < 0.001, early vs. midpregnancy). Again, the changes were similar in pregnancies with a normal or an adverse outcome.


CONCLUSIONS
The balance of prostacyclin and thromboxane A(2) shifted in an unfavorable direction in pregnancies complicated by PIH. ASA had a favorable effect on the prostanoids.
Vainio
Merja
M
Department of Obstetrics and Gynecology, Hyvinkää Hospital, Hyvinkää, Finland. merja.vainio@hus.fi
Riutta
Asko
A
Koivisto
Anna-Maija
AM
Mäenpää
Johanna
J
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives* / Q000652:urine; D001241:Aspirin / Q000008:administration & dosage*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy* / Q000652:urine; D008137:Longitudinal Studies; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy* / Q000652:urine; D011256:Pregnancy Outcome; D018566:Pregnancy, High-Risk; D011453:Prostaglandins / Q000378:metabolism; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D011464:Epoprostenol; D001241:Aspirin