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.
Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, St. Mary's Hospital, Manchester M13 9WL, UK.
Int J Mol Sci. 2021 Apr 26;22(9):4500. doi: 10.3390/ijms22094500.
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 ( < 0.001), and in both normal ( < 0.001) and FGR ( < 0.01) CPVs. Vasorelaxation to SNP was also potentiated by hypoxia in both normal ( < 0.0001) and FGR ( < 0.01) CPVs. However, compared to vessels from normal pregnancies, CPVs from FGR pregnancies showed significantly lower reactivity to SNP ( < 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.
一氧化氮（NO）在控制胎盘中血管张力方面至关重要，它维持着高流量低阻力的循环，有利于氧气和营养物质输送给胎儿。胎盘中血流减少与妊娠并发症有关，也是胎儿生长受限（FGR）的主要原因之一。膳食硝酸盐还原为亚硝酸盐，进而生成 NO，可能为体内提供另一种 NO 来源。我们之前的研究表明，亚硝酸盐可诱导正常妊娠胎盘血管舒张，且在缺氧条件下这种作用增强。在此，我们旨在确定亚硝酸盐是否也可作为 FGR 的血管扩张剂。我们采用血管张力测定法，在常氧和缺氧条件下，评估亚硝酸盐对正常和 FGR 妊娠胎盘绒毛板动脉（CPAs）和静脉（CPVs）的舒张作用，并平行评估一氧化氮供体硝普钠（SNP）的反应。同时测量胎儿血浆中的硝酸盐和亚硝酸盐浓度。缺氧显著增强了 FGR CPAs 对亚硝酸盐的舒张作用（<0.001），并增强了正常（<0.001）和 FGR（<0.01）CPVs 对亚硝酸盐的舒张作用。缺氧也增强了正常（<0.0001）和 FGR（<0.01）CPVs 对 SNP 的舒张作用。然而，与正常妊娠的血管相比，FGR 妊娠的 CPVs 对 SNP 的反应性明显降低（<0.01）。正常和 FGR 妊娠胎儿血浆中硝酸盐和亚硝酸盐浓度无差异。综上所述，这些数据表明，FGR 中存在亚硝酸盐介导的血管舒张，提示靶向该途径的干预措施有可能改善 FGR 妊娠中的胎盘中血流。
