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Amino Acids

, Volume 47, Issue 9, pp 1715–1727 | Cite as

The role of arginine, homoarginine and nitric oxide in pregnancy

  • Asma KhalilEmail author
  • Lotte Hardman
  • Pat O´Brien
Review Article
Part of the following topical collections:
  1. Homoarginine, Arginine and Relatives

Abstract

Normal pregnancy leads to profound maternal hemodynamic changes, including increased blood volume and vasodilatation. Several vasodilator mediators are implicated, including prostaglandins, carbon monoxide and nitric oxide (NO). Pre-eclampsia (PE) affects 3–10 % of pregnancies and is associated with increased maternal and perinatal morbidity and mortality. Around 8 % of pregnancies are complicated by intra-uterine growth restriction (IUGR), also associated with increased perinatal mortality and morbidity. PE and IUGR often co-exist. NO is essential for the formation of healthy endothelium, and in pregnancy promotes endovascular invasion by the cytotrophoblast. As interstitial trophoblasts invade the maternal spiral arteries in the uterine wall, they produce NO which acts on artery walls to create a low-resistance, high-caliber uteroplacental unit. If this process fails, the result is a high-resistance uteroplacental circulation. The hypoperfused and ischemic placenta releases antiangiogenic factors which mediate generalized endothelial dysfunction, oxidative stress and inflammatory mediators. It is these mediators that are implicated in both the fetal and maternal syndromes of PE and IUGR. Studies of NO and its modulator amino acids, including the precursors arginine and homoarginine and the NO synthesis inhibitor asymmetric dimethylarginine (ADMA), have investigated their role in both normal and pathological pregnancies. Many studies of PE (and, to a lesser extent, IUGR) have investigated maternal circulating ADMA, arginine and homoarginine levels. This article reviews and discusses the role of these amino acids in pregnancy. The results have shed some light on their role in these pathologies, but some of the findings have been conflicting and more research is needed. Nevertheless, therapeutic interventions that manipulate these guanidine–amino acids and their interactions hold real promise for the management of pregnancies complicated by PE and/or IUGR, and the results of ongoing studies are eagerly awaited.

Keywords

ADMA Arginine Homoarginine Nitric oxide Pregnancy Pre-eclampsia 

Abbreviations

ADMA

Asymmetric dimethylarginine

cGMP

Cyclic guanosine monophosphate

DDAH

Dimethylarginine dimethylaminohydrolase

ELISA

Enzyme-linked immunosorbent assay

eNOS

Endothelial nitric oxide synthase

FMD

Flow-mediated dilatation

GC–MS

Gas chromatography–mass spectrometry

GC–MS/MS

Gas chromatography–tandem mass spectrometry

GTN

Glyceryl trinitrate

HPLC

High-performance liquid chromatography

ISDN

Isosorbide dinitrate

IUGR

Intra-uterine growth restriction

LC–MS/MS

Liquid chromatography–tandem mass spectrometry

NO

Nitric oxide

NOS

Nitric oxide synthase

PE

Pre-eclampsia

PlGF

Placental growth factor

ROS

Reactive oxygen species

sEng

Soluble endoglin

sFlt-1

Soluble Fms-like tyrosine kinase-1

SGA

Small for gestational age

sGC

Soluble guanylyl cyclase

TRPC

Transient receptor potential cation (channels)

VEGF

Vascular endothelial growth factor

Notes

Conflict of interest

None of the authors has any conflict of interest.

Ethical standard

All studies reported here were approved by the local ethics committees.

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  1. 1.Department of Obstetrics and GynaecologySt. George’s Hospital, St.George’s Healthcare NHS TrustLondonUK
  2. 2.Institute for Women’s HealthUniversity College LondonLondonUK

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