Low-dose aspirin. II. Relationship of angiotensin II pressor responses, circulating eicosanoids, and pregnancy outcome

Forty pregnant women (28 to 32 weeks' gestation) were given low-dose aspirin therapy (81 mg/day) from the time of enrollment until delivery; circulating eicosanoid levels and angiotensin II pressor responses were measured before and after 1 week of aspirin therapy. Subsequent clinical outcome was correlated with these results. All women had significant reductions in serum and plasma thromboxane B₂ levels with aspirin treatment (p < 0.01). Eleven women who remained sensitive to the pressor effects of angiotensin II (effective pressor dose < 10 ng/kg/min) after 1 week of low-dose aspirin treatment exhibited significant decreases (p < 0.05) in plasma 6-keto-prostaglandin F_1α (264 ± 119 vs 161 ± 31 pg/ml, mean ± SD) and prostaglandin E₂ (476 ± 174 vs 351 ± 112 pg/ml) levels. In contrast, patients who were either nonsensitive (refractory) to angiotensin II (n = 18; ≥ 10 ng/kg/min) before aspirin or became nonsensitive after aspirin administration (n = 11) had no change in either plasma 6-keto-prostaglandin F_1α or prostaglandin E₂ concentrations. The occurrence of pregnancy-induced hypertension was 100% in the women who remained angiotensin II sensitive during aspirin therapy as compared with 36% and 39% in the other two groups (χ² = 16.14; p < 0.001). Thus during low-dose aspirin therapy a failure to develop refractoriness to infused angiotensin II is associated with a nonselective inhibition of eicosanoids and the almost certain development of pregnancy-induced hypertension. These observations may reflect a basic defect in vascular adaptation to pregnancy.