PLACENTAL ALTERATIONS AND INTRAUTERINE GROWTH-RETARDATION ASSOCIATED WITH ENALAPRIL EXPOSURE IN EARLY, MID, AND LATE PREGNANCY IN THE RAT

Objective: To identify the stage of placental development in which ena lapril 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 pre gnancy; rats drinking only water served as control. At day 20 of pregn ancy, rats were sacrificed, fetuses and placentas weighed, and placent as examined double-blind by light microscopy. Main Outcome: Both place ntal morphology and fetal weights were altered in early, mid, and late pregnancy. Results: Placentas of enalapril-treated animals more frequ ently showed foci of parallel cords and hypocellular pattern than thos e of controls (66% vs. 28%). Fetal weights of all treated groups were smaller than control (P < .05). Group E8-16 had smaller fetuses and pl acentas (P < .05), and more altered placental structure (83%) than rem aining groups. Conclusion: This study demonstrates that enalapril is a ssociated with decreased fetal growth and placental structural alterat ions, more marked during the mid pregnancy stage of active placentatio n but also present in early and late pregnancy.