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Article

Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction

1
Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9WL, UK
2
Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, St. Mary’s Hospital, Manchester M13 9WL, UK
3
Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm, Sweden
*
Authors to whom correspondence should be addressed.
Academic Editor: Daniel Henrion
Int. J. Mol. Sci. 2021, 22(9), 4500; https://doi.org/10.3390/ijms22094500
Received: 22 March 2021 / Accepted: 21 April 2021 / Published: 26 April 2021
(This article belongs to the Special Issue Molecular Vascular Physiology)
Nitric oxide (NO) is essential in the control of fetoplacental vascular tone, maintaining a high flow−low resistance circulation that favors 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). The 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 vasorelaxation in placental blood vessels from normal pregnancies, and that this effect is enhanced under conditions of hypoxia. Herein, we aimed to determine whether nitrite could 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. View Full-Text
Keywords: pregnancy; fetal growth restriction; placental insufficiency; placenta; chorionic plate vessels; nitric oxide; nitrite; vasorelaxation pregnancy; fetal growth restriction; placental insufficiency; placenta; chorionic plate vessels; nitric oxide; nitrite; vasorelaxation
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MDPI and ACS Style

Tropea, T.; Nihlen, C.; Weitzberg, E.; Lundberg, J.O.; Wareing, M.; Greenwood, S.L.; Sibley, C.P.; Cottrell, E.C. Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction. Int. J. Mol. Sci. 2021, 22, 4500. https://doi.org/10.3390/ijms22094500

AMA Style

Tropea T, Nihlen C, Weitzberg E, Lundberg JO, Wareing M, Greenwood SL, Sibley CP, Cottrell EC. Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction. International Journal of Molecular Sciences. 2021; 22(9):4500. https://doi.org/10.3390/ijms22094500

Chicago/Turabian Style

Tropea, Teresa, Carina Nihlen, Eddie Weitzberg, Jon O. Lundberg, Mark Wareing, Susan L. Greenwood, Colin P. Sibley, and Elizabeth C. Cottrell 2021. "Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction" International Journal of Molecular Sciences 22, no. 9: 4500. https://doi.org/10.3390/ijms22094500

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