Enhanced nitrite-mediated relaxation of placental blood vessels exposed to hypoxia is preserved in pregnancies complicated by fetal growth restriction

Teresa Tropea, Carina Nihlen, Eddie Weitzberg, Jon O. Lundberg, Mark Wareing, Susan Greenwood, Colin Sibley, Elizabeth Cottrell

Research output: Contribution to journalArticlepeer-review

Abstract

Nitric oxide (NO) is essential in the control of fetoplacental vascular tone, maintaining a high flow-low resistance circulation that favours oxygen and nutrient delivery to the fetus. Reduced fetoplacental blood flow is associated with pregnancy complications and is one of the major causes of fetal growth restriction (FGR). Reduction of dietary nitrate to nitrite and subsequently NO may provide an alternative source of NO in vivo. We have previously shown that nitrite induces vaso-relaxation in placental blood vessels from normal pregnancies, and that this effect is enhanced under conditions of hypoxia. Herein, we aimed to determine whether nitrite can also act as a vasodilator in FGR. Using wire myography, vasorelaxant effects of nitrite were assessed on pre-constricted chorionic plate arteries (CPAs) and veins (CPVs) from normal and FGR pregnancies under normoxic and hypoxic conditions. Responses to the NO donor, sodium nitroprusside (SNP), were assessed in parallel. Nitrate and nitrite concentrations were measured in fetal plasma. Hypoxia significantly enhanced vasorelaxation to nitrite in FGR CPAs (p < 0.001), and in both normal (p < 0.001) and FGR (p < 0.01) CPVs. Vasorelaxation to SNP was also potentiated by hypoxia in both normal (p < 0.0001) and FGR (p < 0.01) CPVs. However, compared to vessels from normal pregnancies, CPVs from FGR pregnancies showed significantly lower reactivity to SNP (p < 0.01). Fetal plasma concentrations of nitrate and nitrite were not different between normal and FGR pregnancies. Together, these data show that nitrite-mediated vasorelaxation is preserved in FGR, suggesting that interventions targeting this pathway have the potential to improve fetoplacental blood flow in FGR pregnancies.
Original languageEnglish
JournalInternational Journal of Molecular Sciences
DOIs
Publication statusPublished - 26 Apr 2021

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