Effects of oligomeric grape seed proanthocyanidins on L‐NAME‐induced hypertension in pregnant mice: Role of oxidative stress and endothelial dysfunction

Abstract

The aim of this study was to investigate the effects of Grape Seed Proanthocyanidins (GSP) on Nω-Nitro-L-arginine methyl ester-induced hypertension in pregnant mice. Fifty Kunming mice were randomized into control, control + GSP, model, and model + GSP. Three weeks later, the artery systolic blood pressure was examined and the related pathological changes were detected. Aorta relaxation function was assessed by aorta ring apparatus. Blood urea nitrogen and serum creatinine were measured by an automatic biochemistry analyzer. Colorimetric analysis, enzyme-linked immunosorbent assay, immunofluorescence, and western blot were applied to detect related indicator in serum, cardiac, and kidney tissues. The results showed that GSP treatment for 3 weeks could improve cardiovascular and kidney remodeling indexes and decrease blood urea nitrogen and serum creatinine content in serum, as well as could ameliorate oxidative stress status and endothelial dysfunction. Therefore, it is for the first time found that GSP exerts protective effect against Nω-Nitro-L-arginine methyl ester-induced hypertension in pregnant mice, which provided a theoretical basis for potential application in the clinic.

Grape Seed Extract Polyphenols Improve Resistance Artery Function in Pregnant eNOS–/– Mice

“…However, in addition to placental oxidative stress and impaired placental function ( Myatt and Cui, 2004 ; Burton, 2009 ), an excessive production of ROS has been associated with the pathophysiology of many maternal hypertensive pregnancy-related complications, such as PE ( Myatt and Cui, 2004 ; Burton and Jauniaux, 2011 ; Matsubara et al, 2015 ; Chiarello et al, 2020 ; San Juan-Reyes et al, 2020 ). In agreement with recently published data in the L-NAME mouse model ( Zhu et al, 2018 ), we found that circulating concentrations of MDA were increased in the maternal plasma of eNOS –/– mice compared with WT control groups, and that treatment with GSEP significantly reduced this marker of lipid peroxidation in the hypertensive strain. One significant limitation of this study is mouse plasma volume availability, as investigation of several relevant biomarkers in addition to MDA, are needed to address a complete evaluation of oxidative stress in both maternal and fetal samples.…”

“…In addition, a previous preclinical study investigated the effect of intragastric administration of GSEP in pregnancy, using the L-NAME-induced hypertensive mouse model. The authors measured SBP under anesthesia and demonstrated that treatment with GSEP reversed the hypertensive effect induced by L-NAME after 3 weeks of intervention (Zhu et al, 2018). In agreement with this finding, the current study showed a significant blood pressure-lowering effect of maternal supplementation with GSEP in pregnant eNOS −/− mice.…”

“…Taken together, our data indicate that maternal supplementation with GSEP could offer a cheap and widely available treatment to improve maternal vascular health in hypertensive pregnancies. Protective effects of GSEP against vascular dysfunction have been attributed to their antioxidant properties (Wang et al, 2010;Okudan et al, 2011;Pinna et al, 2017;Zhu et al, 2018;Sato et al, 2020). Furthermore, the treatment did not have adverse effects on fetal outcome and the potential for GSEP as a therapy for complications of chronic hypertension in pregnancy is worthy of further research.…”

“…Grape seed extract polyphenols (GSEP), a complex mixture mainly composed of polymers of catechin ( Shi et al, 2003 ), have a great potential for protection against oxidative stress ( Bagchi et al, 2000 ). Evidence from previous studies in non-pregnant humans, non-pregnant and pregnant animals suggests that commercially available GSEP provide a natural source of antioxidants, which can protect endothelial function and reduce blood pressure ( Oueslati et al, 2016 ; Park et al, 2016 ; Pons et al, 2016 ; Zhu et al, 2018 ). These beneficial effects, in addition to improved cardiovascular and kidney remodeling, have been previously demonstrated in pregnant mice, using the Nω-Nitro-l-arginine methyl ester (L-NAME)-induced hypertension model ( Zhu et al, 2018 ).…”

“…Evidence from previous studies in non-pregnant humans, non-pregnant and pregnant animals suggests that commercially available GSEP provide a natural source of antioxidants, which can protect endothelial function and reduce blood pressure ( Oueslati et al, 2016 ; Park et al, 2016 ; Pons et al, 2016 ; Zhu et al, 2018 ). These beneficial effects, in addition to improved cardiovascular and kidney remodeling, have been previously demonstrated in pregnant mice, using the Nω-Nitro-l-arginine methyl ester (L-NAME)-induced hypertension model ( Zhu et al, 2018 ). However, to date there have been no reports on the effects of GSEP supplementation in pregnancy on maternal resistance artery (diameter < 300 μm) function or pregnancy outcomes, in an animal model of chronic hypertension.…”