System y ⁺ Arginine Transport and NO Production in Peripheral Blood Mononuclear Cells in Pregnancy and Preeclampsia

Abstract

Abstract-Systemic inflammation and oxidative stress are features of normal pregnancy and, in excess, contribute to the pathogenesis of preeclampsia. Inflammatory cell activation stimulates uptake of arginine (the precursor for nitric oxide) by transport system y ϩ , expression of one of its genes (CAT-2) together with inducible nitric oxide synthase, leading to nitric oxide production. We investigated whether these changes occur in peripheral blood mononuclear cells in normal pregnancy and are exaggerated in preeclampsia. Samples from matched trios of nonpregnant, normal pregnant, and preeclamptic women were studied. Arginine transport was characterized, and the expression of inducible nitric oxide synthase and cell-specific nitric oxide production were measured. Arginine uptake by system y ϩ was significantly increased (PϽ0.001) in peripheral blood mononuclear cells in normal pregnancy but not in preeclampsia. CAT-2 mRNA was not detected in cells from nonpregnant women but was detected in 3 of 10 normal pregnant and 8 of 10 of preeclamptic women (PϽ0.001). Inducible nitric oxide synthase protein expression was significantly increased in normal pregnant women (PϽ0.05) but not preeclamptic women. No significant differences in cell-specific nitric oxide production were observed. These changes confirm the predictions for normal pregnancy but not for preeclampsia in which, despite increases in CAT-2 expression, arginine uptake is not additionally increased. This may create a relative deficiency of arginine in PBMCs favoring superoxide and peroxynitrite production and contribute to oxidative and nitrosative stress in preeclampsia.

L-Arginine Transport and Nitric Oxide Synthesis in Human Endothelial Progenitor Cells

“…As reported in undifferentiated cells 29,30 and in differentiated cells such as human peripheral blood mononuclear cells 39,40 or HUVEC, 5 our study suggests functional presence of y + L system in both hEPC-3d and hEPC14d. Remarkably, transport activity associated to this system was about 300 times higher in hEPC-14d compared with 3 days cultured cells.…”

L-arginine transport and nitric oxide synthesis in human endothelial progenitor cells

“…As reported in undifferentiated cells, 29,30 as well as in differentiated cells such as human peripheral blood mononuclear cells, 39,40 or HUVEC 5 our study suggests functional presence of y + L system in both hEPC-3d and hEPC-14d.…”

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

“…Recently, Noris et al 34 suggested that L-arginine depletion, caused by arginase II overexpression, may orient NO synthase toward oxidant species in placenta in preeclampsia. In addition, McCord and colleagues 35 reported that a relative deficiency of arginine in peripheral blood mononuclear cells may favor superoxide and peroxynitrite production and contribute to oxidative and nitrosative stress in preeclampsia. In a study by Conrad and colleagues, 25 under conditions that were carefully monitored to reflect endogenous production and not dietary intake, there was no evidence for a decrease in NO production by measure of plasma or urinary excretion of nitrite and nitrate.…”