TY - JOUR
T1 - Sustained captopril-induced reduction in blood pressure is associated with alterations in Gut-Brain axis in the spontaneously hypertensive rat
AU - Yang, Tao
AU - Aquino, Victor
AU - Lobaton, Gilberto O.
AU - Li, Hongbao
AU - Colon-Perez, Luis
AU - Goel, Ruby
AU - Qi, Yanfei
AU - Zubcevic, Jasenka
AU - Febo, Marcelo
AU - Richards, Elaine M.
AU - Pepine, Carl J.
AU - Raizada, Mohan K.
N1 - Funding Information:
This work was supported by NIH grants R01 HL132448 and HL033610.
Publisher Copyright:
© 2019 The Authors.
PY - 2019
Y1 - 2019
N2 - 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 genesequencing– 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.
AB - 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 genesequencing– 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.
KW - Angiotensin-converting enzyme inhibitor
KW - Antihypertensive agent
KW - Blood pressure
KW - Brain imaging
KW - Brain-gut axis
KW - Gut microbiota
KW - Hypertension
UR - http://www.scopus.com/inward/record.url?scp=85061485610&partnerID=8YFLogxK
U2 - 10.1161/JAHA.118.010721
DO - 10.1161/JAHA.118.010721
M3 - Article
C2 - 30755073
AN - SCOPUS:85061485610
SN - 2047-9980
VL - 8
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 4
M1 - e010721
ER -