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Reduced transport of amino acids from mother to fetus can lead to fetal intrauterine growth restriction (IUGR). The activities of several amino acid transport systems, including system A, are decreased in placental syncytiotrophoblast of IUGR pregnancies. [Na.sup.+]-[K.sup.+]-ATPase activity provides an essential driving force for [Na.sup.+]-coupled system A transport, is decreased in the placenta of IUGR pregnancies, and is decreased by angiotensin II in several tissues. Several reports have shown activation of the fetoplacental renin-angiotensin system (RAS) in IUGR. We investigated the effect of angiotensin II on placental system A transport and [Na.sup.+] -[K.sup.+]-ATPase activity in placental villi. Placental system A activity in single primary villous fragments was measured as the [Na.sup.+]-dependent uptake of [alpha]-(methylamino)isobutyric acid, and [Na.sup.+]/[K.sup.+] ATPase activity was measured as ouabain-sensitive uptake of [sup.86]rubidium. Angiotensin II decreased system A activity in a concentration-dependent fashion (10-500 nmol/l). Angiotensin II type 1 receptor (AT1-R) antagonists losartan and AT1-R anti-peptide blocked the angiotensin II effect, but the angiotensin II type 2 receptor antagonist PD-123319 was without effect. System A activity was not altered by preincubation with AT1-R-independent vasoconstrictors, and antioxidants did not prevent the decrease in activity mediated by angiotensin II. Angiotensin II decreased [Na.sup.+]-[K.sup.+]-ATPase activity by an AT1-R dependent mechanism, and inhibition of [Na.sup.+]-[K.sup.+]-ATPase activity decreased system A activity in a dose-response fashion. These data suggest that angiotensin II, via AT1-R signaling, decreases system A activity by suppressing [Na.sup.+]-[K.sup.+]-ATPase in human placental villi, consistent with possible adverse effects of enhanced placental RAS on fetal growth. fetal intrauterine growth restriction; preeclampsia; ouabain; [Na.sup.+] -[K.sup.+]-ATPase; [sup.86]rubidium; angiotensin II type I receptor

Human placental growth and vascularization reveal the possible participation of endothelin-1 (ET-1) due to the potent mitogenic and vasoactive characteristics of ET-1 and the occurrence of its receptor in third trimester placenta. Each trimester of pregnancy is examined on the basis of the properties and quantities of the placental ET receptors. The period after pregnancy yields villous human placenta in three different trimesters, allowing the synthesis of particulates with rich membranes. Radio ligand saturation studies, ligand competition and reverse transcription-polymerase chain reaction are used to determine the properties of the ET receptors, and to analyze the concentration, affinity and specificity of ET binding sites.