Dietary interventions for fetal growth restriction - therapeutic potential of dietary nitrate supplementation in pregnancy

Elizabeth Cottrell, Teresa Tropea, Laura Ormesher, Susan Greenwood, Mark Wareing, Edward Johnstone, Jenny Myers, Colin Sibley, Elizabeth Cottrell, Teresa Tropea, Laura Ormesher, Susan Greenwood, Mark Wareing, Edward Johnstone, Jenny Myers, Colin Sibley

Abstract

Fetal growth restriction (FGR) affects around 5% of pregnancies and is associated with significant short- and long-term adverse outcomes. A number of factors can increase the risk of FGR, one of which is poor maternal diet. In terms of pathology, both clinically and in many experimental models of FGR, impaired uteroplacental vascular function is implicated, leading to a reduction in the delivery of oxygen and nutrients to the developing fetus. Whilst mechanisms underpinning impaired uteroplacental vascular function are not fully understood, interventions aimed at enhancing nitric oxide (NO) bioavailability remain a key area of interest in obstetric research. In addition to endogenous NO production from the amino acid l-arginine, via nitric oxide synthase (NOS) enzymes, research in recent years has established that significant NO can be derived from dietary nitrate, via the 'alternative NO pathway'. Dietary nitrate, abundant in green leafy vegetables and beetroot, can increase NO bioactivity, conferring beneficial effects on cardiovascular function and blood flow. Given the beneficial effects of dietary nitrate supplementation to date in non-pregnant humans and animals, current investigations aim to assess the therapeutic potential of this approach in pregnancy to enhance NO bioactivity, improve uteroplacental vascular function and increase fetal growth.

Keywords: fetal growth restriction; nitrate supplementation; pregnancy.

© 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Figures

Figure 1. Canonical NO–cGMP signalling pathway in…
Figure 1. Canonical NO–cGMP signalling pathway in vascular tissues
Nitric oxide (produced from endogenous NOS pathways, or via reduction of dietary nitrate) binds a prosthetic haem group on sGC to activate the enzyme, leading to synthesis of the second messenger cGMP. Increased intracellular cGMP leads ultimately to smooth muscle cell hyperpolarisation and vasodilatation. Activity through this pathway is attenuated via the actions of PDE‐5, which degrades cGMP. Agents such as sildenafil citrate, which inhibits the PDE‐5 enzyme, can enhance NO–cGMP signalling by prolonging the elevation of intracellular cGMP.

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