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

Journal of the American Heart Association - Tập 8 Số 4 - 2019
Tao Yang1, Victor Aquino2, Gilberto O. Lobaton3, Hong‐Bao Li4,5, Luis M. Colon‐Perez6, Ruby Goel7, Yanfei Qi8, Jasenka Zubcevic9, Marcelo Febo10, Elaine M. Richards11, Carl J. Pepine12, Mohan K. Raizada13
1Tao Yang Department of Physiology and Functional Genomics, , College of Medicine, , University of Florida, , Gainesville, , FL
2Victor Aquino Department of Physiology and Functional Genomics, , College of Medicine, , University of Florida, , Gainesville, , FL
3Gilberto O. Lobaton Department of Physiology and Functional Genomics, , College of Medicine, , University of Florida, , Gainesville, , FL
4Department of Physiology and Pathophysiology School of Basic Medical Sciences Xi'an Jiaotong University Xi'an China
5Hongbao Li Department of Physiology and Functional Genomics, , College of Medicine, , University of Florida, , Gainesville, , FL Department of Physiology and Pathophysiology, , School of Basic Medical Sciences, , Xi'an Jiaotong University, , Xi'an, , China
6Department of Psychiatry College of Medicine University of Florida Gainesville FL
7Ruby Goel Department of Physiology and Functional Genomics, , College of Medicine, , University of Florida, , Gainesville, , FL
8Yanfei Qi Division of Cardiovascular Medicine, , University of Florida, , Gainesville, , FL
9Jasenka Zubcevic Department of Physiological Sciences, , College of Veterinary Medicine, , University of Florida, , Gainesville, , FL
10Marcelo Febo Department of Psychiatry, , College of Medicine, , University of Florida, , Gainesville, , FL
11Elaine M. Richards Department of Physiology and Functional Genomics, , College of Medicine, , University of Florida, , Gainesville, , FL
12Carl J. Pepine Division of Cardiovascular Medicine, , University of Florida, , Gainesville, , FL
13Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL

Tóm tắt

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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Journal of the American Heart Association

Tập 8 Số 4

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