Angiotensin II decreases system A amino acid transporter activity in human placental villous fragments through AT1 receptor activation.

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(+)-K(+)-ATPase activity provides an essential driving force for Na(+)-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(+)-K(+)-ATPase activity in placental villi. Placental system A activity in single primary villous fragments was measured as the Na(+)-dependent uptake of alpha-(methylamino)isobutyric acid, and Na(+)/K(+) ATPase activity was measured as ouabain-sensitive uptake of (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(+)-K(+)-ATPase activity by an AT1-R dependent mechanism, and inhibition of Na(+)-K(+)-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(+)-K(+)-ATPase in human placental villi, consistent with possible adverse effects of enhanced placental RAS on fetal growth.