Fiche publication
Date publication
décembre 2017
Journal
Hypertension research : official journal of the Japanese Society of Hypertension
Auteurs
Membres identifiés du Cancéropôle Est :
Pr SCHINI-KERTH Valérie
,
Dr AUGER Cyril
Tous les auteurs :
Niazi ZR, Silva GC, Ribeiro TP, León-González AJ, Kassem M, Mirajkar A, Alvi A, Abbas M, Zgheel F, Schini-Kerth VB, Auger C
Lien Pubmed
Résumé
Eicosapentaenoic acid:docosahexaenoic acid (EPA:DHA) 6:1, an omega-3 polyunsaturated fatty acid formulation, has been shown to induce a sustained formation of endothelial nitric oxide (NO) synthase-derived NO, a major vasoprotective factor. This study examined whether chronic intake of EPA:DHA 6:1 prevents hypertension and endothelial dysfunction induced by angiotensin II (Ang II) in rats. Male Wister rats received orally corn oil or EPA:DHA 6:1 (500 mg kg per day) before chronic infusion of Ang II (0.4 mg kg per day). Systolic blood pressure was determined by tail cuff sphingomanometry, vascular reactivity using a myograph, oxidative stress using dihydroethidium and protein expression by immunofluorescence and western blot analysis. Ang II-induced hypertension was associated with reduced acetylcholine-induced relaxations of secondary branch mesenteric artery rings affecting the endothelium-dependent hyperpolarization (EDH)- and the NO-mediated relaxations, both of which were improved by the NADPH oxidase inhibitor VAS-2870. The Ang II treatment induced also endothelium-dependent contractile responses (EDCFs), which were abolished by the cyclooxygenase (COX) inhibitor indomethacin. An increased level of vascular oxidative stress and expression of NADPH oxidase subunits (p47 and p22), COX-1 and COX-2, endothelial NO synthase and Ang II type 1 receptors were observed in the Ang II group, whereas SK and connexin 37 were downregulated. Intake of EPA:DHA 6:1 prevented the Ang II-induced hypertension and endothelial dysfunction by improving both the NO- and EDH-mediated relaxations, and by reducing EDCFs and the expression of target proteins. The present findings indicate that chronic intake of EPA:DHA 6:1 prevented the Ang II-induced hypertension and endothelial dysfunction in rats, most likely by preventing NADPH oxidase- and COX-derived oxidative stress.
Mots clés
Angiotensin II, Animals, Antihypertensive Agents, chemistry, Drug Evaluation, Preclinical, Endothelium, Vascular, drug effects, Fatty Acids, Omega-3, chemistry, Hypertension, chemically induced, Male, NADPH Oxidases, metabolism, Nitric Oxide, metabolism, Oxidative Stress, drug effects, Random Allocation, Rats, Wistar
Référence
Hypertens. Res.. 2017 Dec;40(12):966-975
