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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/E1009    most recent 00134.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Shibata, E. Articles by Hubel, C. A. Search for Related Content PubMed PubMed Citation Articles by Shibata, E. Articles by Hubel, C. A.

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

¹Magee-Womens Research Institute and ²Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh School of Medicine; ³Department of Epidemiology and ⁴Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh Pennsylvania

Submitted 21 March 2006 ; accepted in final form 14 June 2006

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 -(methylamino)isobutyric acid, and Na⁺/K⁺ ATPase activity was measured as ouabain-sensitive uptake of ⁸⁶rubidium. 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.

fetal intrauterine growth restriction; preeclampsia; ouabain; Na⁺-K⁺-ATPase; ⁸⁶rubidium; angiotensin II type 1 receptor

This article has been cited by other articles:

				M. Snook Parrott, F. von Versen-Hoeynck, R. B. Ness, N. Markovic, and J. M. Roberts System A Amino Acid Transporter Activity in Term Placenta Is Substrate Specific and Inversely Related to Amino Acid Concentration Reproductive Sciences, October 1, 2007; 14(7): 687 - 693. [Abstract] [PDF]