Pregnancies complicated by chronic hypertension have an increased risk of adverse perinatal outcomes ( Gilbert et al., 2007 Chappell et al., 2008), including fetal growth restriction (FGR), preterm delivery, and perinatal death ( Jain, 1997 Sibai et al., 1998 Bramham et al., 2014), as well as life-threatening maternal consequences, such as preeclampsia (PE), superimposed PE, eclampsia, cerebral hemorrhage, and maternal death ( Sibai, 2002 Bateman et al., 2006 Bellamy et al., 2007 Moodley, 2008). Maternal supplementation with GSEP may be a safe intervention to improve outcomes in pregnancies associated with hypertension and vascular dysfunction. Our data suggest that GSEP improve resistance artery function, potentially through antioxidant actions, and provide a basis to further investigate these beneficial effects including in the prevention of intracerebral hemorrhage. Supplementation with GSEP had no effect in WT mice and did not affect fetal outcomes in either genotype. Whilst there was no effect of GSEP on vascular reactivity of aortas, GSEP improved endothelial-dependent relaxation in mesenteric and uterine arteries of eNOS –/– mice ( P < 0.05 and P < 0.001, respectively) and normalized lumen diameters of pressurized posterior cerebral arteries in eNOS –/– mice ( P < 0.001).
GSEP reduced maternal SBP ( P < 0.01) and plasma MDA concentrations ( P < 0.01) in eNOS –/– mice. At GD17.5, maternal systolic blood pressure (SBP) was measured at GD18.5, maternal malondialdehyde (MDA) concentrations, vascular function of aortic, mesenteric, uterine and posterior cerebral arteries was assessed, and fetal outcome evaluated. Pregnant C57BL/6J (WT) and eNOS –/– mice received either GSEP (200 mg/kg/day) or drinking water, between gestational (GD) day 10.5 and GD18.5. We tested the hypothesis that administration of GSEP during pregnancy would reduce oxidative stress and improve resistance artery function with no detrimental effects on fetal growth, in an established model of maternal hypertension associated with vascular dysfunction, the endothelial NO synthase knockout (eNOS –/–) mouse. Grape seed extract polyphenols (GSEP) have been suggested to promote cardiovascular protection, at least in part through antioxidant actions. Increased oxidative stress is known to contribute to poor vascular function however, trials of antioxidant supplementation have raised concerns about fetal outcomes, including risk of low birthweight. Hypertension during pregnancy is a leading cause of maternal and fetal morbidity and mortality worldwide, increasing the risk of complications including preeclampsia, intracerebral hemorrhage and fetal growth restriction. Mary’s Hospital, Manchester, United Kingdom 2Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, St.1Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, Maternal and Fetal Health Research Centre, University of Manchester, Manchester, United Kingdom.
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