Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction
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...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-04-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/9/4500 |
id |
doaj-80e288e6e92949b8bdf93714ca41f436 |
---|---|
record_format |
Article |
spelling |
doaj-80e288e6e92949b8bdf93714ca41f4362021-04-26T23:01:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01224500450010.3390/ijms22094500Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth RestrictionTeresa Tropea0Carina Nihlen1Eddie Weitzberg2Jon O. Lundberg3Mark Wareing4Susan L. Greenwood5Colin P. Sibley6Elizabeth C. Cottrell7Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9WL, UKDepartment of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm, SwedenDepartment of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm, SwedenDepartment of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm, SwedenMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9WL, UKMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9WL, UKMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9WL, UKMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9WL, UKNitric 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 (<i>p</i> < 0.001), and in both normal (<i>p</i> < 0.001) and FGR (<i>p</i> < 0.01) CPVs. Vasorelaxation to SNP was also potentiated by hypoxia in both normal (<i>p</i> < 0.0001) and FGR (<i>p</i> < 0.01) CPVs. However, compared to vessels from normal pregnancies, CPVs from FGR pregnancies showed significantly lower reactivity to SNP (<i>p</i> < 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.https://www.mdpi.com/1422-0067/22/9/4500pregnancyfetal growth restrictionplacental insufficiencyplacentachorionic plate vesselsnitric oxide |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Teresa Tropea Carina Nihlen Eddie Weitzberg Jon O. Lundberg Mark Wareing Susan L. Greenwood Colin P. Sibley Elizabeth C. Cottrell |
spellingShingle |
Teresa Tropea Carina Nihlen Eddie Weitzberg Jon O. Lundberg Mark Wareing Susan L. Greenwood Colin P. Sibley Elizabeth C. Cottrell 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 pregnancy fetal growth restriction placental insufficiency placenta chorionic plate vessels nitric oxide |
author_facet |
Teresa Tropea Carina Nihlen Eddie Weitzberg Jon O. Lundberg Mark Wareing Susan L. Greenwood Colin P. Sibley Elizabeth C. Cottrell |
author_sort |
Teresa Tropea |
title |
Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction |
title_short |
Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction |
title_full |
Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction |
title_fullStr |
Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction |
title_full_unstemmed |
Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction |
title_sort |
enhanced nitrite-mediated relaxation of placental blood vessels exposed to hypoxia is preserved in pregnancies complicated by fetal growth restriction |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-04-01 |
description |
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 (<i>p</i> < 0.001), and in both normal (<i>p</i> < 0.001) and FGR (<i>p</i> < 0.01) CPVs. Vasorelaxation to SNP was also potentiated by hypoxia in both normal (<i>p</i> < 0.0001) and FGR (<i>p</i> < 0.01) CPVs. However, compared to vessels from normal pregnancies, CPVs from FGR pregnancies showed significantly lower reactivity to SNP (<i>p</i> < 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. |
topic |
pregnancy fetal growth restriction placental insufficiency placenta chorionic plate vessels nitric oxide |
url |
https://www.mdpi.com/1422-0067/22/9/4500 |
work_keys_str_mv |
AT teresatropea enhancednitritemediatedrelaxationofplacentalbloodvesselsexposedtohypoxiaispreservedinpregnanciescomplicatedbyfetalgrowthrestriction AT carinanihlen enhancednitritemediatedrelaxationofplacentalbloodvesselsexposedtohypoxiaispreservedinpregnanciescomplicatedbyfetalgrowthrestriction AT eddieweitzberg enhancednitritemediatedrelaxationofplacentalbloodvesselsexposedtohypoxiaispreservedinpregnanciescomplicatedbyfetalgrowthrestriction AT jonolundberg enhancednitritemediatedrelaxationofplacentalbloodvesselsexposedtohypoxiaispreservedinpregnanciescomplicatedbyfetalgrowthrestriction AT markwareing enhancednitritemediatedrelaxationofplacentalbloodvesselsexposedtohypoxiaispreservedinpregnanciescomplicatedbyfetalgrowthrestriction AT susanlgreenwood enhancednitritemediatedrelaxationofplacentalbloodvesselsexposedtohypoxiaispreservedinpregnanciescomplicatedbyfetalgrowthrestriction AT colinpsibley enhancednitritemediatedrelaxationofplacentalbloodvesselsexposedtohypoxiaispreservedinpregnanciescomplicatedbyfetalgrowthrestriction AT elizabethccottrell enhancednitritemediatedrelaxationofplacentalbloodvesselsexposedtohypoxiaispreservedinpregnanciescomplicatedbyfetalgrowthrestriction |
_version_ |
1721507293358456832 |