Asymmetric Dimethylarginine, an Endogenous Inhibitor of Nitric Oxide Synthase, in Maternal and Fetal Circulation

Abstract

Pronounced dilation of the maternal vasculature occurs during normal pregnancy. Likewise, low resistance characterizes the fetoplacental circulation. Nitric oxide released by endothelial cells is a potent vasodilator known to be a key modulator of both maternal and fetal vascular tone. However, the mechanisms underlying the maternal circulatory adaptations and the low resistance of the fetal circulation remain unknown. The aim of the present study was to compare levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in the maternal and fetal circulations. High performance liquid chromatography was used to measure asymmetric ADMA in the maternal and umbilical venous plasma. Plasma ADMA levels during the first trimester were 0.29 +/- 0.05, the third trimester before term 0.29 +/- 0.05, and at term 0.32 +/- 0.05 nmol/mL, which were significantly (P <.05) lower than the levels measured in nonpregnant women (0.41 +/- 0.06 nmol/mL). By contrast, ADMA levels in umbilical venous plasma averaged 1.02 +/- 0.18 nmol/mL, significantly (P <.005) higher than maternal levels. Unlike ADMA, levels of plasma L-arginine, the nitric oxide precursor, did not significantly differ among nonpregnant and pregnant women and the fetus.During pregnancy, maternal hemodynamics are modulated, at least in part, by a reduction in ADMA. Conversely, the low resistance to umbilical blood flow is maintained despite substantially higher fetal ADMA levels. Thus, the predominant mechanisms regulating the maternal and fetal circulation apparently differ.

Determination of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in umbilical blood

“…Maeda et al [7] showed that ADMA concentrations in umbilical venous blood were significantly higher than the maternal values, but that L-arginine concentrations were not significantly different from the maternal values. Mittermayer et al [8] reported that male preterm newborns had significantly higher umbilical venous blood concentrations of ADMA than did female preterm newborns and term newborns of both sexes.…”

“…Determination of ADMA concentrations in umbilical blood might be important to elucidate the regulatory mechanisms of the circulatory system in this particular period. Only 3 studies have measured umbilical blood concentrations of ADMA [7][8][9]. Asymmetric dimethylarginine in umbilical blood appears significantly higher than the maternal levels when delivery occurs at term or preterm.…”

Sildenafil Stimulates and Dexamethasone Inhibits Pulmonary Vascular Development in Congenital Diaphragmatic Hernia Rat Lungs

“…Sildenafil was co-administrated with L -arginine, a NO precursor, to optimize levels of cGMP in the fetal lung, given that in the fetal circulation there is endogenous inhibition of NOS [19]. Without L -arginine, sildenafil may not maintain high levels of cGMP prenatally, due to inhibition of PDE-5.…”

“…Sildenafil was co-administered with L -arginine, a substrate of eNOS, to ensure optimal levels of cGMP in the fetal lung, since at early stages of pregnancy endogenous NOS inhibition can be found [19]. …”

The Role of ADMA in Various Diseases

“…52 Whether ADMA has a role in normal pregnancies remains undetermined. Maeda, et al, 57 discovered that maternal concentrations of ADMA were lower in normal pregnancies than in non-pregnant women, indicating that ADMA is essential for vasodilation during pregnancy. Recently, Saarelainen, et al, 58 have cast doubt on the role of ADMA as a critical regulator of blood pressure in normal pregnancy.…”