Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects.
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
23
04
2019
revised:
21
11
2019
accepted:
06
12
2019
pubmed:
29
12
2019
medline:
22
6
2021
entrez:
29
12
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND AND PURPOSE
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.
EXPERIMENTAL APPROACH
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.
KEY RESULTS
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.
CONCLUSION AND IMPLICATIONS
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.
Identifiants
pubmed: 31883108
doi: 10.1111/bph.14965
pmc: PMC7161554
doi:
Substances chimiques
Antihypertensive Agents
0
RNA, Ribosomal, 16S
0
Losartan
JMS50MPO89
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2006-2023Subventions
Organisme : Fondo Europeo de Desarrollo Regional FEDER
Pays : International
Organisme : Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad
ID : SAF2017-84894-R
Pays : International
Organisme : Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad
ID : SAF2014-55523-R
Pays : International
Organisme : Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad
ID : AGL2015-67995-C3
Pays : International
Organisme : Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad
ID : AGL2015-67995-C3-3-R
Pays : International
Organisme : Ministerio de Economia y Competitividad, Instituto de Salud Carlos III
ID : CIBER-CV
Pays : International
Organisme : Ministerio de Economia y Competitividad, Instituto de Salud Carlos III
ID : CIBER-EHD
Pays : International
Organisme : Junta de Andalucía
ID : P12-CTS-2722
Pays : International
Organisme : Junta de Andalucía
ID : AGR-6826
Pays : International
Organisme : Junta de Andalucía
ID : CTS-164
Pays : International
Informations de copyright
© 2019 The British Pharmacological Society.
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