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Beetroot juice lowers blood pressure and improves endothelial function in pregnant eNOS-/- mice: importance of nitrate-independent effects

Tropea, T; Renshall, LJ; Nihlen, C; Weitzberg, E; Lundberg, JO; David, AL; Tsatsaris, V; ... Cottrell, EC; + view all (2020) Beetroot juice lowers blood pressure and improves endothelial function in pregnant eNOS-/- mice: importance of nitrate-independent effects. The Journal of Physiology , 598 (18) pp. 4079-4092. 10.1113/JP279655. Green open access

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Abstract

Maternal hypertension is associated with adverse pregnancy outcomes, including fetal growth restriction (FGR), due in part to reductions in nitric oxide (NO) bioavailability. We hypothesized that maternal dietary nitrate administration would increase NO bioavailability to reduce systolic blood pressure (SBP), improve vascular function and increase fetal growth in pregnant endothelial NO synthase knockout (eNOS−/−) mice, which exhibit hypertension, endothelial dysfunction and FGR. Pregnant wildtype (WT) and eNOS−/− mice were supplemented with nitrate‐containing beetroot juice (BRJ+) from gestational day (GD) 12.5. Control mice received an equivalent dose of nitrate‐depleted BRJ (BRJ−) or normal drinking water. At GD17.5, maternal SBP was measured; at GD18.5, maternal nitrate/nitrite concentrations, uterine artery (UtA) blood flow and endothelial function were assessed, and pregnancy outcomes were determined. Plasma nitrate concentrations were increased in both WT and eNOS−/− mice supplemented with BRJ+ (P < 0.001), whereas nitrite concentrations were increased only in eNOS−/− mice (P < 0.001). BRJ− did not alter nitrate/nitrite concentrations. SBP was lowered and UtA endothelial function was enhanced in eNOS−/− mice supplemented with either BRJ+ or BRJ−, indicating nitrate‐independent effects of BRJ. Improvements in endothelial function in eNOS−/− mice were abrogated in the presence of 25 mm KCl, implicating enhanced EDH signalling in BRJ− treated animals. At GD18.5, eNOS−/− fetuses were significantly smaller than WT animals (P < 0.001), but BRJ supplementation did not affect fetal weight. BRJ may be a beneficial intervention in pregnancies associated with hypertension, endothelial dysfunction and reduced NO bioavailability. Our data showing biological effects of non‐nitrate components of BRJ have implications for both interpretation of previous findings and in the design of future clinical trials.

Type: Article
Title: Beetroot juice lowers blood pressure and improves endothelial function in pregnant eNOS-/- mice: importance of nitrate-independent effects
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1113/JP279655
Publisher version: https://doi.org/10.1113/JP279655
Language: English
Additional information: Copyright © 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10097827
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