In the dose range of 0.5-2.0 mg/kg, acetylsalicylic acid does not affect prostacyclin production in hypertensive pregnancies

Objective. To determine the dose of acetylsalicylic acid (ASA), that inhibi ts the production of the vasoconstrictive, aggregatory thromboxane A(2) whi le sparing the production of the vasodilatory antiaggregatory prostacyclin. Design. A controlled study comparing the effects of three doses of ASA on t he production of thromboxane A(2) and prostacyclin. Methods. Seven pregnant hypertensive patients and five non-pregnant healthy women received 0.5, 1.0 and 2.0 mg/kg/day of ASA, each dose for 10-12 days , the treatment periods following each other immediately. Seven normotensiv e pregnant women served as controls and were given no ASA. Blood and urine samples were taken at baseline and after the treatment periods to determine serum thromboxane B-2 and the urinary 2.3-dinor-6-ketoprostaglandin F-1 al pha and 11-dehydrothromboxaneB(2), the major stable metabolites of prostacy clin and thromboxane A(2), respectively Results. The urinary excretion of 11-dehydrothromboxaneB(2) was significant ly higher in both hypertensive (34.9+/-18.3 pg/mu mol creatinine) and normo tensive (39.3+/-14.4 pg/mu mol creatinine) pregnant women than in non-pregn ant women (14.8+/-6.4 pg/mu mol creatinine). The urinary excretion of 2.3-d inor-6-ketoprostaglandinF(1 alpha) was also higher in normotensive pregnant women (93.9+/-50.9 pg/mu mol creatinine) than in non-pregnant women (18.2/-11.3 pg/mu mol creatinine). The excretion rate of 2.3-dinor-6-ketoprostag landinF(1 alpha) in hypertensive patients was lower than in normotensive pr egnant women (44.7+/-24.2 pg/mu mol creatinine). At baseline the urinary 2. 3-dinor-6-ketoprostaglandin F-1 alpha/11-dehydrothromboxaneB(2) ratio was a lmost the same in the hypertensive patients (1.6) and in the non-pregnant w omen (1.2). The ratio was 2.6 in normotensive pregnant women. In the hypertensive group , already the lowest dose of ASA inhibited urinary 11-dehydrothromboxaneB(2 ) excretion significantly. Because none of the doses of ASA inhibited 2.3-d inor-6-ketoprostaglandinF(1 alpha) production, the 2.3-dinor-6-ketoprostagl andinF(1 alpha)/11-dehydrothromboxaneB(2) ratio was shifted in the favor of prostacyclin at all dose levels. In the non-pregnant women, even the highe st dose level of ASA failed to affect the ratio. Conclusion. In the dose range of 0.5-2.0 mg/kg/day, ASA has a favorable eff ect on the ratio of prostacyclin to thromboxane A(2) in hypertensive pregna ncies.