Angiotensin II (AT1) vascular binding sites in human placentae from normal-term, preeclamptic and growth retarded pregnancies.
Angiotensin II (ANG II) is a potent vasoconstrictor in isolated human placental cotyledons and may contribute to the regulation of fetoplacental perfusion. We have used quantitative in vitro receptor autoradiography to examine antagonist ((Sar1,Ile8)-[125I]ANG II) and agonist ligand ([125I]ANG II) binding sites in normal-term, preeclamptic and fetal (intrauterine) growth retarded pregnancies. A similar distribution of binding sites was demonstrated using both ligands, localized to blood vessels in placental villi. Binding density was inversely related to vessel size, being significantly greater on microvessels in distal regions of the villous tree than on proximal vessels in main stem villi. Binding sites exhibited the characteristics of the AT1 class of ANG II receptor, ligand binding being sensitive to dithiothreitol, completely inhibited by nonpeptide AT1 antagonists (Losartan, EXP3174 and SKF108566) and not inhibited by the AT2 antagonist (PD123319). Guanine nucleotides also inhibited [125I]ANG II binding and abolished the high affinity component of agonist inhibition of (Ser1,Ile8)-[125I]ANG II binding, indicating G protein coupling. The capacity and affinity of the binding sites were significantly lower in placentae from pregnancies complicated by preeclampsia and intrauterine growth retardation compared to that in normal-term controls. These differences were apparently not due to prior receptor occupancy by endogenous ligand, but may reflect activation of the placental renin-angiotensin system and receptor down-regulation. Locally generated ANG II, acting via AT1 receptors, may contribute to the regulation of fetoplacental blood flow and influence placental perfusion in preeclamptic and growth retarded pregnancies.
Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
G A
GA
Knock
M H
MH
Sullivan
A
A
McCarthy
M G
MG
Elder
J M
JM
Polak
J
J
Wharton
D000804:Angiotensin II / Q000378:metabolism*; D001345:Autoradiography; D001665:Binding Sites; D001808:Blood Vessels / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011945:Receptors, Angiotensin / Q000032:analysis*
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D006160:Guanosine Triphosphate