Captopril: Association with Fetal Death and Pulmonary Vascular Changes in the Rabbit

Captopril (D-3-mercapto-2-methylpropanoyl-L-proline) has recently been approved for the treatment of refractory systemic hypertension. Administration of this agent has been shown experimentally to decrease circulating levels of angiotensin II and to increase levels of bradykinin and prostaglandins. In order to examine the effect on the pulmonary vasculature of the neonate, captopril was administered to rabbits from the middle of pregnancy to term, at doses comparable to those used in man. Fetal death in 20 treated rabbits was 86%, in contrast to 1% in 12 control rabbits. Some of the rabbits were made hypoxic in a hypobaric chamber (522 mm Hg pressure) during the period of captopril administration. Under these conditions, captopril administered to the maternal rabbits had a demonstrable cardiopulmonary effect in the neonates, as demonstrated by a significant reduction in pulmonary arteriolar medial thickness and both left and right ventricular weights compared to the hypoxic untreated controls. In view of these observations it would be prudent to avoid using captopril for the treatment of hypertension during pregnancy, until the mechanism of fetal death and the reasons for species variation are known.