Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects.

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  • Additional Information
    • Affiliation:
      Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
      Gene Regulation in Cardiovascular Remodeling and Inflammation Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
      Ciber de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
      Instituto de Investigación Biosanitaria de Granada, ibs. GRANADA, Granada, Spain
    • Abstract:
      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.
    • Journal Subset:
      Biomedical; Europe; Peer Reviewed; UK & Ireland
    • ISSN:
      0007-1188
    • MEDLINE Info:
      PMID: NLM31883108 NLM UID: 7502536
    • Grant Information:
      CIBER-EHD//Ministerio de Economia y Competitividad, Instituto de Salud Carlos III/; SAF2014-55523-R//Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad/; AGL2015-67995-C3-3-R//Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad/; CIBER-CV//Ministerio de Economia y Competitividad, Instituto de Salud Carlos III/; P12-CTS-2722//Junta de Andalucía/; //Fondo Europeo de Desarrollo Regional FEDER/; AGR-6826//Junta de Andalucía/; AGL2015-67995-C3//Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad/; CTS-164//Junta de Andalucía/; SAF2017-84894-R//Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad/
    • Publication Date:
      In Process
    • Publication Date:
      20200428
    • DOI:
      10.1111/bph.14965
    • Accession Number:
      142768052
  • Citations
    • ABNT:
      ROBLES, V. I. et al. Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects. British Journal of Pharmacology, [s. l.], v. 177, n. 9, p. 2006–2023, 2020. DOI 10.1111/bph.14965. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=142768052. Acesso em: 1 dez. 2020.
    • AMA:
      Robles VI, Toral M, Visitación N, et al. Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects. British Journal of Pharmacology. 2020;177(9):2006-2023. doi:10.1111/bph.14965
    • APA:
      Robles, V. I., Toral, M., Visitación, N., Sánchez, M., Gómez, G. M., Muñoz, R., Algieri, F., Vezza, T., Jiménez, R., Gálvez, J., Romero, M., Redondo, J. M., Duarte, J., Robles-Vera, I., de la Visitación, N., & Gómez-Guzmán, M. (2020). Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects. British Journal of Pharmacology, 177(9), 2006–2023. https://doi.org/10.1111/bph.14965
    • Chicago/Turabian: Author-Date:
      Robles, Vera, Iñaki, Marta Toral, Néstor Visitación, Manuel Sánchez, Guzmán, Manuel Gómez, Raquel Muñoz, Francesca Algieri, et al. 2020. “Changes to the Gut Microbiota Induced by Losartan Contributes to Its Antihypertensive Effects.” British Journal of Pharmacology 177 (9): 2006–23. doi:10.1111/bph.14965.
    • Harvard:
      Robles, V. I. et al. (2020) ‘Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects’, British Journal of Pharmacology, 177(9), pp. 2006–2023. doi: 10.1111/bph.14965.
    • Harvard: Australian:
      Robles, VI, Toral, M, Visitación, N, Sánchez, M, Gómez, GM, Muñoz, R, Algieri, F, Vezza, T, Jiménez, R, Gálvez, J, Romero, M, Redondo, JM, Duarte, J, Robles-Vera, I, de la Visitación, N & Gómez-Guzmán, M 2020, ‘Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects’, British Journal of Pharmacology, vol. 177, no. 9, pp. 2006–2023, viewed 1 December 2020, .
    • MLA:
      Robles, Vera, Iñaki, et al. “Changes to the Gut Microbiota Induced by Losartan Contributes to Its Antihypertensive Effects.” British Journal of Pharmacology, vol. 177, no. 9, May 2020, pp. 2006–2023. EBSCOhost, doi:10.1111/bph.14965.
    • Chicago/Turabian: Humanities:
      Robles, Vera, Iñaki, Marta Toral, Néstor Visitación, Manuel Sánchez, Guzmán, Manuel Gómez, Raquel Muñoz, Francesca Algieri, et al. “Changes to the Gut Microbiota Induced by Losartan Contributes to Its Antihypertensive Effects.” British Journal of Pharmacology 177, no. 9 (May 2020): 2006–23. doi:10.1111/bph.14965.
    • Vancouver/ICMJE:
      Robles VI, Toral M, Visitación N, Sánchez M, Gómez GM, Muñoz R, et al. Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects. British Journal of Pharmacology [Internet]. 2020 May [cited 2020 Dec 1];177(9):2006–23. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=142768052