Abstract

Vascular aging is characterized by functional and structural changes of the vessel wall, including endothelial dysfunction, with decreased endothelial NO· bioavailability and elevated vasoconstrictor and inflammatory mediator production, vascular rigidity, and tone impairment. Moringa oleifera (MOI) is a little tree, and different parts of which are used in traditional medicine in tropical Africa, America, and Asia for therapeutic applications in several disorders including cardiovascular disease. The present study is aimed at assessing the effect of MOI on aging-associated alteration of the endothelial function in Wistar rats. Middle-aged Wistar rats (46-week-old males) have been fed with food containing or not 750 mg/kg/day of MOI seed powder for 4 weeks. A group of young Wistar rats (16-week-old) was used as control. Measurement of isometric contraction, western blot analysis, and immunostaining has then been performed in the aortas and mesenteric arteries to assess the endothelium function. MOI treatment improved carbachol-induced relaxation in both aortas and mesenteric arteries of middle-aged rats. In the aortas, this was associated with an increased Akt signalling and endothelial NO synthase activation and a downregulation of arginase-1. In the mesenteric arteries, the improvement of the endothelial-dependent relaxation was related to an EDHF-dependent mechanism. These results suggest a vascular protective effect of MOI seeds against the vascular dysfunction that develops during aging through different mechanisms in conductance and resistance arteries.

Highlights

  • Vascular aging corresponds to functional and structural changes of the arterial wall characterized by endothelial dysfunction and vascular rigidity [1, 2]

  • Vascular aging consists of a set of changes in the mechanical and structural properties of the vascular wall including a decrease in endothelium-dependent relaxation by reducing the bioavailability of NO⋅ and/or EDHF depending on the arterial bed [4, 10, 22]

  • The endothelial effect of dietary Moringa oleifera (MOI) on the EDHF pathway is probably due to the polyphenolic compounds contained in MOI seeds, in agreement with the polyphenolic compound-related antioxidant and anti-inflammatory effects of a diet containing MOI seeds that we previously described [18]

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Summary

Introduction

Vascular aging corresponds to functional and structural changes of the arterial wall characterized by endothelial dysfunction and vascular rigidity [1, 2]. A primary mechanism responsible for aging-induced endothelial dysfunction is the decrease in the bioavailability and the production of nitric oxide (NO⋅), mainly resulting from the increased oxidative stress. BH4 reduction can result in eNOS uncoupling, leading to the generation of ROS rather than NO⋅ and perpetuating endothelial dysfunction [5]. Increased arginase expression and activity are involved in endothelial dysfunction in aged vessels [6, 7]. Since arginase and eNOS compete for their common L-arginine (L-Arg) substrate, a rise in arginase activity or expression limits endothelial NO⋅ production in the vasculature [6,7,8]. The increased methylation of L-Arg and the resulting production of dimethyl L-Arg, observed in aged rats and humans, contribute to the inhibition of eNOS activity [9]

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