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Effet des précurseurs de monoxyde d'azote sur la fonction vasculaire et la performance à l'exercice

Abstract : Primary and secondary prevention of cardiovascular diseases is a major public health concern. Cardiovascular prevention is mainly underpinned by the control of cardiovascular risks. Among them, arterial hypertension (30% of adults in France) and sedentarity (40% of french population) represents two main targets in cardiovascular prevention. Endothelial function as well as exercise tolerance and performance (fitness status) are used as powerful markers of cardiovascular morbidity-mortality.A normal vasomotor endothelial function allows to regulate vascular tone. By synthesising vasoactive substances, vascular endothelium continuously maintains an optimal balance between vasodilation and vasoconstriction to match oxygen and energetic substrate supply to the demand. Endothelial function is plastic, and is increased for instance by physical activity and decreased with age. Endothelial dysfunction is essentially characterized by the production of less vasodilation substances, inducing an increase in blood pressure, arterial stiffness and leading to blood-tissue exchanges alterations. Degrees of endothelial dysfunction is considered as a cardiovascular risk marker.One major vasoactive substance is nitric oxide (NO), which is produced by NO-synthase (NOS) in endothelium, and is a mediator of smooth muscle cells relaxation. This major endogen synthesis can be complemented by NO synthesis from simple reduction of nitrite to NO. Several mechanisms are provided to explain a decrease in NO endothelial synthesis, including decrease of enzymatic activity (NOS) and/or an inadequate substrate or cofactor bioavailability. This decrease in NO bioavailability can be offset, either by NOS activity optimization, or increase NO bioavailability at a vascular level. Although the effects of NO precursor supplementation on health and exercise performance have been extensively studied, results are somehow controversial, mainly due to methodological discrepancies. Thus, the real interest of these types of interventions stays unclear.Thought this thesis work, we were interested to physiological effect in healthy subjects of different interventions which may increase NO bioavailability at vascular level. Focusing on food supplement consumption, we differentiated two NO precursor, two supplementation modalities, and two populations.We have assessed effect of increasing NO bioavailability by acute or chronic supplementation of both NOS-dependent (L-arginine, L-citrulline) and/or NOS-independent (nitrate) pathways, with or without simultaneous training program, in young and older healthy subjects, on vascular function and exercise performances.In healthy young individuals, NO precursor intake increase endothelial function assessed by post-ischemic vasodilation, without effect neither on arterial pressure and fitness nor on exercise performances. However, nitrate and citrulline supplementation increase exercise training effect on maximal strength and strength endurance. In healthy older adults, chronic intake of nitrate and citrulline reduce arterial pressure and improve maximal aerobic power by decrease of submaximal VO2 and heart rate.
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Thibault Le Roux-Mallouf. Effet des précurseurs de monoxyde d'azote sur la fonction vasculaire et la performance à l'exercice. Santé. Université Grenoble Alpes, 2018. Français. ⟨NNT : 2018GREAS049⟩. ⟨tel-02893415⟩

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