The effect of captopril (SQ14,225) upon mother and fetus in the chronically cannulated ewe and in the pregnant rabbit

Abstract

1. An inhibitor of angiotensin-I-converting enzyme activity (D-3-mercapto-2-methylpropanoyl-L-proline, Captopril) was given to five chronically cannulated pregnant ewes and eleven rabbits in late pregnancy. 2. Within 2 min of administration to the sheep, Captopril had blocked the maternal conversion of angiotensin I to II, as assessed by the pressor response evoked by the i.v. administration of angiotensin I. Maternal and fetal basal systemic blood pressures had fallen within 10 min of administration. Although maternal systemic blood pressure returned to basal levels within 2 hr, fetal pressures remained low for up to 2 days. 3. All ewes went into spontaneous labour at or near term. One lamb was live-born but very weak and failed to establish suckling. The remaining seven lambs were fresh still-births. 4. Gestation length was significantly prolonged in the treated rabbits by comparison with ten controls. The still-birth rate was 37% in the treated animals and 6% in the controls (P less than 0.001). 5. It is concluded that the administration of Captopril to the two species studied is harmful to the fetus. The observations suggest that the drug rapidly crosses the placenta, and may cross the blood-brain barrier to exert a central effect. It may also interfere with the normal initiation of parturition.