Effect of low-dose aspirin on vascular refractoriness in angiotensin-sensitive primigravid women.

The hypothesis that an enhanced vasopressor response to angiotensin II in pregnancy may be corrected by suppressing production of platelet thromboxane A2 with low-dose aspirin was tested in a randomized, placebo-controlled, double-blind trial. We studied 36 normotensive primigravid women with an elevated blood pressure response to intravenously infused angiotensin II at 28 weeks' gestation; 18 women received 60 mg of aspirin daily and the same number received matched placebo until 34 weeks' gestation, when angiotensin-sensitivity was again determined. In women taking aspirin, values of thrombin-induced platelet malondialdehyde production were approximately 10% of those determined in the placebo group, indicating marked suppression of thromboxane A2 synthesis. In the aspirin group vascular refractoriness to angiotensin II was restored in 14 of 17 treated women, by comparison with 5 of 15 women in the placebo group who had remained normotensive. These results support the hypothesis that prostacyclin/thromboxane imbalance is an important pathophysiologic factor in the development of the enhanced angiotensin-sensitivity associated with pregnancy-induced hypertensive disorders.

Prediction of pregnancy-induced hypertensive disorders by angiotensin II sensitivity and supine pressor test.

An angiotensin II sensitivity test and a supine pressor test were done consecutively at 28 weeks gestation in 90 healthy, normotensive nulliparous women. None of the supine pressor tests was positive, applying the predefined threshold of a rise of 20 mmHg in diastolic blood pressure after rolling over; nine tests were positive using a corrected 9 mmHg cut-off level. Ten women had a positive angiotensin sensitivity test using a threshold of the effective pressor dose of 8 ng/kg/min; 22 women were positive using an effective pressor dose of less than or equal to 10 ng/kg/min. Later in pregnancy 12 women (13%) developed pregnancy-induced hypertensive disease (PIH). The specificity of both tests of predicting the development of PIH was about 90%. The sensitivity of the angiotensin sensitivity test at the 10 ng/kg/min level was 92%. Because of its low sensitivity of 25% the supine pressor test appears to have no value for the prediction of PIH. There was a significant positive association between angiotensin II refractoriness and birthweight.

Source of plasma prorenin in early and late pregnancy: observations in a patient with primary ovarian failure.

The plasma levels of enzymatically active renin (active renin) and inactive renin (prorenin) were measured in a woman with primary ovarian failure, in whom pregnancy was established by the induction of an artificial cycle and in vitro fertilization of a donated oocyte fertilized with the sperm of her husband. The results were compared with those in nine normal pregnant women. Prepregnancy plasma active renin and prorenin levels were normal in the patient. Active renin rose 2-fold during pregnancy in both the patient and the normal pregnant women. In the first 8 weeks of pregnancy prorenin rose by 156 microU/mL in the patient, whereas it rose by 869 +/- 169 microU/mL (mean +/- SD) in the normal pregnant women. Thus, the rise in prorenin in our patient was much less than normal. Prorenin remained abnormally low throughout the pregnancy, which lasted 40 weeks. Therefore, the high prorenin levels that occur normally during pregnancy may depend on normal ovarian function. Amniotic fluid prorenin in the patient was similar to that in normal pregnant women and was 75 times higher than that in plasma. This finding suggests that prorenin production by the chorionic cells was normal in the patient and that chorionic prorenin does not contribute in any major degree to the level of prorenin in maternal plasma. Because of these findings and in light of recent evidence that the ovary secretes prorenin and produces high plasma prorenin levels in women with hyperstimulated cycles, we conclude that the ovary is the main source of the elevated plasma prorenin levels in pregnant women.

Low-dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae.

The possibility of preventing pregnancy-induced hypertension (PIH) and pre-eclampsia in primigravidae by suppressing production of thromboxane A2 with low-dose aspirin was investigated in a randomised, placebo-controlled, double-blind trial. 46 normotensive women at 28 weeks' gestation, judged to be at risk of PIH or pre-eclampsia because of an increased blood-pressure response to intravenously infused angiotensin II, were studied. 23 women received 60 mg aspirin daily, and the same number received matching placebo until delivery. In the placebo group PIH, pre-eclampsia, and eclampsia developed in 4, 7, and 1 cases, respectively, whereas only 2 women in the aspirin group had mild PIH. There were no adverse effects of treatment in mothers or infants. Low-dose aspirin may restore prostacyclin/thromboxane imbalance, previously suggested as an important aetiological factor in PIH and pre-eclampsia.