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.