The Probiotic Lactobacillus fermentum Prevents Dysbiosis and Vascular Oxidative Stress in Rats with Hypertension Induced by Chronic Nitric Oxide Blockade

Molecular Nutrition and Food Research - Tập 62 Số 19 - 2018
Iñaki Robles‐Vera1, Marta Toral1, Néstor de la Visitación1, Manuel Sánchez1,2, Miguel Romero1,2, Mónica Olivares3, Rosario Jiménez4,1,2, Juan Duarte5,1,2
1Department of Pharmacology, School of Pharmacy, University of Granada, 18071 Granada, Spain
2Instituto de Investigación Biosanitaria de Granada 18012 Granada Spain
3Laboratorio de Descubrimiento y Preclínica Departamento de Investigación BIOSEARCH S.A. 18004 Granada Spain
4CIBERCV 18071 Granada Spain
5Centro de Investigaciones Biomedicas (CIBM) 18100 Granada Spain

Tóm tắt

ScopeWhether the probiotic Lactobacillus fermentum CECT5716 (LC40) ameliorates hypertension in rats with chronic nitric oxide (NO) synthase inhibition is tested.Methods and resultsRats are randomly divided into four different groups and treated for 4 weeks: a) vehicle (control), b) vehicle plus NG‐nitro‐l‐arginine methyl ester (l‐NAME; 50 mg 100 mL−1 in drinking water), c) LC40 (109 colony‐forming units d–1 by gavage), and d) LC40 plus l‐NAME. l‐NAME induces gut dysbiosis, characterized mainly by an increased Fimicutes/Bacteroidetes (F/B) ratio and reduced Bifidobacterium content, increased Th17 cells and reduced Treg in mesenteric lymph nodes (MLN), increased aortic Th17 infiltration and reactive oxygen species, reduced aortic endothelium‐dependent relaxant response to acetylcholine, and hypertension. LC40 prevents gut dysbiosis, alters the Th17/Treg balance in MLN, vascular oxidative stress, and inflammation, slightly improves endothelial dysfuncion but do not inhibit the development of l‐NAME‐induced hypertension.ConclusionChronic LC40 treatment, in this model of chronic inhibition of NO synthesis, reduces early events involved in atherosclerosis development, such as vascular oxidative stress and pro‐inflammatory status, as a result of prevention of gut dysbiosis and immune changes in MLN, but not hypertension, confirming the critical role of NO in the antihypertensive effects of LC40 in genetic hypertension.

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Tài liệu tham khảo

10.1016/S0140-6736(03)14739-3

10.3109/08037051.2014.868629

10.1161/CIRCULATIONAHA.116.024545

10.1038/nrgastro.2014.66

10.1161/HYPERTENSIONAHA.114.03469

10.1007/s11906-017-0723-4

10.1016/j.foodres.2015.07.015

10.1002/mnfr.201500290

10.1681/ASN.2015050562

10.1126/science.aad9378

10.1017/S0007114508986876

10.1016/j.imbio.2010.01.004

10.1161/ATVBAHA.111.233262

10.1172/JCI115849

Xu J., 2013, Evid. Based Complement. Alternat. Med., 2013, 809128

10.1161/CIRCRESAHA.115.306539

10.1097/gme.0b013e31802d9785

10.1017/S0007114511004314

10.1161/HYPERTENSIONAHA.111.174490

10.1042/CS20150111

10.1073/pnas.1000080107

Zhou H. W., 2011, I.S.M.E. J., 5, 741

10.3389/fmicb.2017.01687

10.1093/bioinformatics/btv401

10.1128/AEM.00062-07

10.1128/JCM.00845-13

10.1186/gb-2011-12-6-r60

10.1161/HYPERTENSIONAHA.115.05315

10.1126/science.1102901

10.1038/mi.2007.14

10.1002/eji.201040391

10.1007/s12035-016-0066-1

10.1093/cvr/cvs422

10.1152/ajpregu.00051.2012

10.1161/01.HYP.32.6.958

10.1177/0022034514529974

10.1016/j.freeradbiomed.2014.09.017

10.1002/mnfr.201600372

10.1186/s40168-016-0222-x

Kim S., 2018, Clin. Sci. (Lond.), 1470

10.1136/gutjnl-2011-301476

10.1172/JCI95376

10.1172/JCI59150

10.1038/nature11809

10.1172/JCI74084

10.1172/JCI118872

10.1161/01.HYP.21.5.660

10.1097/00004872-199816120-00016

10.1016/j.amjhyper.2005.06.006

10.3920/BM2014.0035

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Molecular Nutrition and Food Research

Tập 62 Số 19

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