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Sustained Captopril‐Induced Reduction in Blood Pressure Is Associated With Alterations in Gut‐Brain Axis in the Spontaneously Hypertensive Rat

BACKGROUND: We have demonstrated that the antihypertensive effect of the angiotensin‐converting enzyme inhibitor, captopril (CAP), is associated with beneficial effects on gut pathology. Coupled with the evidence that CAP exerts prolonged reduction in blood pressure (BP) after discontinuation of tre...

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Autores principales: Yang, Tao, Aquino, Victor, Lobaton, Gilberto O., Li, Hongbao, Colon‐Perez, Luis, Goel, Ruby, Qi, Yanfei, Zubcevic, Jasenka, Febo, Marcelo, Richards, Elaine M., Pepine, Carl J., Raizada, Mohan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405665/
https://www.ncbi.nlm.nih.gov/pubmed/30755073
http://dx.doi.org/10.1161/JAHA.118.010721
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author Yang, Tao
Aquino, Victor
Lobaton, Gilberto O.
Li, Hongbao
Colon‐Perez, Luis
Goel, Ruby
Qi, Yanfei
Zubcevic, Jasenka
Febo, Marcelo
Richards, Elaine M.
Pepine, Carl J.
Raizada, Mohan K.
author_facet Yang, Tao
Aquino, Victor
Lobaton, Gilberto O.
Li, Hongbao
Colon‐Perez, Luis
Goel, Ruby
Qi, Yanfei
Zubcevic, Jasenka
Febo, Marcelo
Richards, Elaine M.
Pepine, Carl J.
Raizada, Mohan K.
author_sort Yang, Tao
collection PubMed
description BACKGROUND: We have demonstrated that the antihypertensive effect of the angiotensin‐converting enzyme inhibitor, captopril (CAP), is associated with beneficial effects on gut pathology. Coupled with the evidence that CAP exerts prolonged reduction in blood pressure (BP) after discontinuation of treatment, we investigate whether persistent beneficial actions of CAP are linked to alterations of gut microbiota and improvement of hypertension‐induced gut pathology. METHODS AND RESULTS: Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats were treated with CAP (250 mg/kg/day) for 4 weeks followed by withdrawal for 16 weeks. Gut microbiota, gut pathology, BP, and brain neuronal activity were assessed. CAP resulted in a ≈60 mm Hg decrease in systolic BP after 3 weeks of treatment in SHR, and the decrease remained significant at least 5 weeks after CAP withdrawal. In contrast, CAP caused modest decrease in systolic BP in Wistar Kyoto. 16S rRNA gene‐sequencing–based gut microbial analyses in SHR showed sustained alteration of gut microbiota and increase in Allobaculum after CAP withdrawal. Phylogenetic investigation of communities by reconstruction of unobserved states analysis revealed significant increase in bacterial sporulation upon CAP treatment in SHR. These were associated with persistent improvement in gut pathology and permeability. Furthermore, manganese‐enhanced magnetic resonance imaging showed significantly decreased neuronal activity in the posterior pituitary of SHR 4 weeks after withdrawal. CONCLUSIONS: Decreased BP, altered gut microbiota, improved gut pathology and permeability, and dampened posterior pituitary neuronal activity were maintained after CAP withdrawal in the SHR. They suggest that CAP influences the brain‐gut axis to maintain the sustained antihypertensive effect of CAP after withdrawal.
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spelling pubmed-64056652019-03-19 Sustained Captopril‐Induced Reduction in Blood Pressure Is Associated With Alterations in Gut‐Brain Axis in the Spontaneously Hypertensive Rat Yang, Tao Aquino, Victor Lobaton, Gilberto O. Li, Hongbao Colon‐Perez, Luis Goel, Ruby Qi, Yanfei Zubcevic, Jasenka Febo, Marcelo Richards, Elaine M. Pepine, Carl J. Raizada, Mohan K. J Am Heart Assoc Original Research BACKGROUND: We have demonstrated that the antihypertensive effect of the angiotensin‐converting enzyme inhibitor, captopril (CAP), is associated with beneficial effects on gut pathology. Coupled with the evidence that CAP exerts prolonged reduction in blood pressure (BP) after discontinuation of treatment, we investigate whether persistent beneficial actions of CAP are linked to alterations of gut microbiota and improvement of hypertension‐induced gut pathology. METHODS AND RESULTS: Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats were treated with CAP (250 mg/kg/day) for 4 weeks followed by withdrawal for 16 weeks. Gut microbiota, gut pathology, BP, and brain neuronal activity were assessed. CAP resulted in a ≈60 mm Hg decrease in systolic BP after 3 weeks of treatment in SHR, and the decrease remained significant at least 5 weeks after CAP withdrawal. In contrast, CAP caused modest decrease in systolic BP in Wistar Kyoto. 16S rRNA gene‐sequencing–based gut microbial analyses in SHR showed sustained alteration of gut microbiota and increase in Allobaculum after CAP withdrawal. Phylogenetic investigation of communities by reconstruction of unobserved states analysis revealed significant increase in bacterial sporulation upon CAP treatment in SHR. These were associated with persistent improvement in gut pathology and permeability. Furthermore, manganese‐enhanced magnetic resonance imaging showed significantly decreased neuronal activity in the posterior pituitary of SHR 4 weeks after withdrawal. CONCLUSIONS: Decreased BP, altered gut microbiota, improved gut pathology and permeability, and dampened posterior pituitary neuronal activity were maintained after CAP withdrawal in the SHR. They suggest that CAP influences the brain‐gut axis to maintain the sustained antihypertensive effect of CAP after withdrawal. John Wiley and Sons Inc. 2019-02-13 /pmc/articles/PMC6405665/ /pubmed/30755073 http://dx.doi.org/10.1161/JAHA.118.010721 Text en © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Yang, Tao
Aquino, Victor
Lobaton, Gilberto O.
Li, Hongbao
Colon‐Perez, Luis
Goel, Ruby
Qi, Yanfei
Zubcevic, Jasenka
Febo, Marcelo
Richards, Elaine M.
Pepine, Carl J.
Raizada, Mohan K.
Sustained Captopril‐Induced Reduction in Blood Pressure Is Associated With Alterations in Gut‐Brain Axis in the Spontaneously Hypertensive Rat
title Sustained Captopril‐Induced Reduction in Blood Pressure Is Associated With Alterations in Gut‐Brain Axis in the Spontaneously Hypertensive Rat
title_full Sustained Captopril‐Induced Reduction in Blood Pressure Is Associated With Alterations in Gut‐Brain Axis in the Spontaneously Hypertensive Rat
title_fullStr Sustained Captopril‐Induced Reduction in Blood Pressure Is Associated With Alterations in Gut‐Brain Axis in the Spontaneously Hypertensive Rat
title_full_unstemmed Sustained Captopril‐Induced Reduction in Blood Pressure Is Associated With Alterations in Gut‐Brain Axis in the Spontaneously Hypertensive Rat
title_short Sustained Captopril‐Induced Reduction in Blood Pressure Is Associated With Alterations in Gut‐Brain Axis in the Spontaneously Hypertensive Rat
title_sort sustained captopril‐induced reduction in blood pressure is associated with alterations in gut‐brain axis in the spontaneously hypertensive rat
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405665/
https://www.ncbi.nlm.nih.gov/pubmed/30755073
http://dx.doi.org/10.1161/JAHA.118.010721
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