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


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.


ADMA Arginine Homoarginine Nitric oxide Pregnancy Pre-eclampsia 



Asymmetric dimethylarginine


Cyclic guanosine monophosphate


Dimethylarginine dimethylaminohydrolase


Enzyme-linked immunosorbent assay


Endothelial nitric oxide synthase


Flow-mediated dilatation


Gas chromatography–mass spectrometry


Gas chromatography–tandem mass spectrometry


Glyceryl trinitrate


High-performance liquid chromatography


Isosorbide dinitrate


Intra-uterine growth restriction


Liquid chromatography–tandem mass spectrometry


Nitric oxide


Nitric oxide synthase




Placental growth factor


Reactive oxygen species


Soluble endoglin


Soluble Fms-like tyrosine kinase-1


Small for gestational age


Soluble guanylyl cyclase


Transient receptor potential cation (channels)


Vascular endothelial growth factor


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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© 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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