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 less than 0.01). Eleven women who remained sensitive to the pressor effects of angiotensin II (effective pressor dose less than 10 ng/kg/min) after 1 week of low-dose aspirin treatment exhibited significant decreases (p less than 0.05) in plasma 6-keto-prostaglandin F1 alpha (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; greater than or equal to 10 ng/kg/min) before aspirin or became nonsensitive after aspirin administration (n = 11) had no change in either plasma 6-keto-prostaglandin F1 alpha 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 (x2 = 16.14; p less than 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.