M. Vainio et al., In the dose range of 0.5-2.0 mg/kg, acetylsalicylic acid does not affect prostacyclin production in hypertensive pregnancies, ACT OBST SC, 78(2), 1999, pp. 82-88
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.