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Changes to the gutmicrobiota induced bylosartan contributesto itsantihypertensiveeffects Iñaki Robles‐VeraMarta ToralNéstor de la Visitación2019 год

Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects
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Аннотация: Hypertension is associated with gut dysbiosis. Here we have evaluated the effects of the angiotensin receptor antagonist losartan on gut microbiota in spontaneously hypertensive rats (SHR) to assess their contribution to its antihypertensive effects.Twenty-week-old Wistar Kyoto rats (WKY) and SHR were treated with losartan for 5 weeks (SHR-losartan). Faecal microbiota transplantation (FMT) was performed from donor SHR-losartan group to recipient untreated-SHR. Blood pressure (BP) was measured using tail-cuff plethysmography. Composition of the gut microbiota was assessed by amplification of the V3-V4 region of 16S rRNA gene. T cells were analysed in gut/aorta by flow cytometry.Faeces from SHR showed gut dysbiosis, characterised by higher Firmicutes/Bacteroidetes ratios, lower acetate- and higher lactate-producing bacteria, and lower levels of strict anaerobic bacteria, effects which were restored to normal by losartan. Improvement of gut dysbiosis was linked to higher colonic integrity and lower sympathetic drive in the gut. In contrast, hydralazine reduced BP, but it neither restored gut dysbiosis nor colonic integrity. FMT from SHR-losartan to SHR reduced BP, improved the aortic endothelium-dependent relaxation to ACh, and reduced NADPH oxidase activity. These vascular changes were accompanied by both increased Treg and decreased Th17 cell populations in the vascular wall.In SHR, losartan treatment reduced gut dysbiosis and sympathetic drive in the gut, thus improving gut integrity. The changes induced by losartan in gut microbiota contributed, in part, to protecting the vasculature and reducing BP, possibly by modulating the immune system in the gut.
Год издания: 2019
Авторы: Iñaki Robles‐Vera, Marta Toral, Néstor de la Visitación, Manuel Sánchez, Manuel Gómez‐Guzmán, Raquel Muñoz, Francesca Algieri, Teresa Vezza, Rosario Jiménez, Júlio Gálvez, Miguel Romero, Juan Miguel Redondo, Juan Duarte
Издательство: Wiley
Источник: British Journal of Pharmacology
Ключевые слова: Gut microbiota and health, Dietary Effects on Health, Diet and metabolism studies
Другие ссылки: British Journal of Pharmacology (HTML)
RISalud Institutional Health Repository of Andalucía (PDF)
RISalud Institutional Health Repository of Andalucía (HTML)
Institutional Repository of the University of Granada (University of Granada) (PDF)
Institutional Repository of the University of Granada (University of Granada) (HTML)
PubMed Central (HTML)
PubMed (HTML)