FOSINOPRIL TREATMENT OF PREGNANT RATS - DEVELOPMENTAL TOXICITY, FETALANGIOTENSIN-CONVERTING ENZYME-INHIBITION, AND FETAL ANGIOTENSIN-II RECEPTOR REGULATION

Pregnant women are advised against using angiotensin-converting enzyme (ACE) inhibitors due to reports of adverse effects on human fetuses. This study examined ACE binding and angiotensin II (Ang II) receptor b inding in fetuses of rats treated with the ACE inhibitor fosinopril (1 6 mg/kg/day fosinopril, p.o. in 4 divided doses, from gestational day (gd) 13 to gd 18). Binding of the potent radiolabeled ACE inhibitor I- 125-351A to ACE in the lung and aorta of gd 19 fetuses of fosinopril-t reated dams was reduced by 56 and 44%, respectively, compared to fetus es from vehicle-treated dams, indicating that fosinopril or its active metabolite, fosinoprilat, crosses the placental barrier and inhibits fetal ACE. Fetal Ang II receptor binding of (125)-Sar(I),Ile(8) Ang II was not altered in most of the tissues examined, although reductions in binding in the adrenal of fetuses of fosinopril-treated dams approa ched statistical significance.