Fosinopril treatment of pregnant rats: developmental toxicity, fetal angiotensin-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 binding in fetuses of rats treated with the ACE inhibitor fosinopril (16 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 125I-351A to ACE in the lung and aorta of gd 19 fetuses of fosinopril-treated dams was reduced by 56 and 44%, respectively, compared to fetuses 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 125I-Sar1,Ile8 Ang II was not altered in most of the tissues examined, although reductions in binding in the adrenal of fetuses of fosinopril-treated dams approached statistical significance.
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D004151:Dipeptides / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism*; D017328:Fosinopril / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism*; D014018:Tissue Distribution
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D011945:Receptors, Angiotensin; C042037:L-proline, N2-((1S)-1-carboxy-3-phenylpropyl)-N6-((4-hydroxyphenyl)iminomethyl)-L-lysyl-; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D000110:Acetylcholinesterase; D017328:Fosinopril