Placental Alterations and Intrauterine Growth Retardation Associated with Enalapril Exposure in Early, MID, and Late Pregnancy in the Rat

Abstract

Objective: To identify the stage of placental development in which enalapril use in the pregnant rat is deleterious.

Methods: Approximately 9 mg/rat/day of enalapril were given in the drinking water to Sprague-Dawley rats on days 1-7 (E1-7), 8-16 (E8-16) and 17-20 (E17-20) of pregnancy; rats drinking only water served as control. At day 20 of pregnancy, rats were sacrificed, fetuses and placentas weighed, and placentas examined double-blind by light microscopy.

Main Outcome: Both placental morphology and fetal weights were altered in early, mid, and late pregnancy.

Results: Placentas of enalapril-treated animals more frequently showed foci of parallel cords and hypocellular pattern than those of controls (66% vs. 28%). Fetal weights of all treated groups were smaller than control (P <. 05). Group E8-16 had smaller fetuses and placentas (P <. 05), and more altered placental structure (83%) than remaining groups.

Conclusion: This study demonstrates that enalapril is associated with decreased fetal growth and placental structural alterations, more marked during the mid pregnancy stage of active placentation but also present in early and late pregnancy.

Key Words:

• Converting enzyme inhibitors
• Intrauterine growth retardation
• Placenta
• Pregnancy