Asymmetric Dimethylarginine in the Maternal and Fetal Circulation in Preeclampsia

Abstract

Preeclampsia is a leading cause of intrauterine growth restriction and preterm birth. Endothelial dysfunction is the common final pathway leading to clinical signs of preeclampsia including hypertension and proteinuria. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS and induces endothelial dysfunction by reversibly inhibiting NO production from L-arginine. The purpose of this study was to investigate maternal and fetal concentrations of ADMA, L-arginine, and symmetric dimethylarginine (SDMA). Women with preeclampsia (n ϭ 47) and controls (n ϭ 51) who gave birth by cesarean section were included in the study. We analyzed the maternal plasma and umbilical vein and artery plasma. We found that not only maternal concentrations of ADMA and SDMA but also L-arginine were significantly higher in women with preeclampsia than in controls. In fetal samples, only SDMA concentrations were higher in the preeclampsia group than in controls. The median ADMA concentration was three times higher in the fetal circulation than in the maternal circulation, but there was no difference between the preeclampsia group and the control group, and the veno-arterious gradient indicated that the placenta was the source of ADMA. (Pediatr Res 66: 411-415, 2009) P reeclampsia is a common pregnancy complication associated with increased risk of preterm birth and fetal growth restriction (1). The exact etiology of preeclampsia is not known, and hence no definitive preventative measures or treatments are available.Endothelial dysfunction is the common final pathway leading to the clinical signs of preeclampsia including hypertension and proteinuria. It is not known to what extent endothelial dysfunction also affects the infant. Increased concentrations of biomarkers for preeclampsia in the maternal circulation are usually not reflected in the infant. Previously, our group has shown that newborns from preeclamptic pregnancies did not differ from those born after uncomplicated pregnancies with respect to circulating biomarkers of inflammation (CRP and calprotectin) (2), and oxidative stress (3), but newborns from preeclamptic pregnancies had elevated concentrations of homocysteine (4).In women with previous preeclampsia, there is an increased risk for cardiovascular disease later in life (5) and an increased risk of hypertension has also been found for their offspring (6,7).It is not clear whether the increased risk in the offspring is caused by the intrauterine environment, shared genes, or impaired intrauterine growth. In epidemiologic and animal studies, low birth weight by itself is associated with an increased risk of cardiovascular disease and metabolic syndrome (8).NO is essential for vascular tone and endothelial function, and elevated circulating concentrations of asymmetric dimethylarginine (ADMA) are associated with reduced vasodilation and endothelial dysfunction (9). ADMA is an endogenous inhibitor of NOS and induces endothelial dysfunction by reversibly inhibiting NO production from L-arginine. The ratio...

Toxic Dimethylarginines: Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA)

“…Despite less attention having been paid to SDMA than to ADMA, there is still a substantial body of research linking elevated SDMA levels to clinical conditions (Table 2) [44,48,56,57,63,64,95,96,97,98,99,100,101,102,103]. As already mentioned, a meta-analysis study showed that SDMA levels correlate well with renal function [44].…”

Pre-eclampsia: Molecular events to biomarkers

“…On the reverse, elevated levels in pre-eclampsia may be due to the impaired formation of vascular components of placenta. 26 Placental hormones are another probable set of predictors for pre-eclampsia. The hormonal role in pregnancy complications has been well reviewed by Reis et al Vascular insufficiency of spiral arteries lead to hypoxia and subsequent hyperplasia of trophoblast.…”

Could ADMA levels in young adults born preterm predict an early endothelial dysfunction?

“…Normally present in blood, ADMA is a strong inhibitor of nitric oxide (NO) synthesis [1,2]. It has long been known that high levels of ADMA are associated with multiple morbid conditions which share the endothelial damage and development typical of atherosclerosis: high cholesterol, smoking, diabetes, hypertension, heart failure, chronic renal failure, erectile dysfunction, preeclampsia, and liver failure [3][4][5][6][7][8][9][10][11]. Furthermore, the predictive power of ADMA has also been demonstrated.…”

“…Exclusion criteria were as follows: 1. presence of pathological conditions known to interfere with ADMA levels; and 2. administration of drugs known to influence ADMA blood concentration [3][4][5][6][7][8][9][10][11]16]. Patients underwent cardiological assessment and BMI was calculated from height and weight.…”