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L-Arginine Transport by the Microvillous Plasma Membrane of the Syncytiotrophoblast from Human Placenta in Relation to Nitric Oxide Production: Effects of Gestation, Preeclampsia, and Intrauterine Growth Restriction

Nuffield Department of Obstetrics and Gynecology (P.T.-Y.A.), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom OX3 9DU; and Academic Unit of Child Health (D.T., S.W.D., J.D.G., C.P.S.) and School of Biological Sciences (C.P.S.), University of Manchester, St. Mary’s Hospital, Manchester, United Kingdom M13 OJH

Address all correspondence and requests for reprints to: Dr. P. Ayuk, Nuffield Department of Obstetrics and Gynecology, John Radcliffe Hospital, Headington, Oxford, United Kingdom OX3 9DU. E-mail: paul.ayuk{at}obs-gyn.ox.ac.uk

Abstract

Nitric oxide (NO) is an important regulator of placental perfusion, and its production is dependent on the activity of substrate (L-arginine) transporters. In the light of evidence for altered NO production in the feto-placental unit in preeclampsia and intrauterine growth restriction (IUGR), we investigated gestational changes in human placental L-arginine transport by systems y⁺ and y⁺L in purified microvillous plasma membrane vesicles. We also examined the effect of preeclampsia and IUGR on the activity of these transport systems and the relationship between transporter activity and NO production (nitrate/nitrite concentrations) in the feto-placental unit. Between first trimester and term, there was a significant positive correlation between system y⁺ activity and gestational age (r = 0.36; P = 0.013; n = 47), but a significant negative correlation between system y⁺L activity and gestational age (r = -0.6; P < 0.0001; n = 47). The activity of these transport systems was not altered in preeclampsia or IUGR. In placentas from normal term pregnancies, there was no correlation between the activity of microvillous plasma membrane L-arginine transporters and nitrate/nitrite concentrations in umbilical venous plasma or placental homogenate.

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