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

ABSTRACT: 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.

SUBMITTER: Yang T

PROVIDER: S-EPMC6405665 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Yang Tao T Aquino Victor V Lobaton Gilberto O GO Li Hongbao H Colon-Perez Luis L Goel Ruby R Qi Yanfei Y Zubcevic Jasenka J Febo Marcelo M Richards Elaine M EM Pepine Carl J CJ Raizada Mohan K MK

Journal of the American Heart Association 20190201 4

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 Spontaneou ...[more]

PMID: 30755073

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Project description:Gut dysbiosis, a pathological imbalance of bacteria, has been shown to contribute to the development of hypertension (HT), systemic- and neuro-inflammation, and blood-brain barrier (BBB) disruption in spontaneously hypertensive stroke prone rats (SHRSP). However, to date individual species that contribute to HT in the SHRSP model have not been identified. One potential reason, is that nearly all studies of the SHRSP gut microbiota have analyzed samples from rats with established HT. The goal of this study was to examine the SHRSP gut microbiota before, during, and after the onset of hypertension, and in normotensive WKY control rats over the same age range. We hypothesized that we could identify key microbes involved in the development of HT by comparing WKY and SHRSP microbiota during the pre-hypertensive state and longitudinally. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and fecal microbiota analyzed by16S rRNA gene sequencing. SHRSP showed significant elevations in SBP, as compared to WKY, beginning at 8 weeks of age (p < 0.05 at each time point). Bacterial community structure was significantly different between WKY and SHRSP as early as 4 weeks of age, and remained different throughout the study (p = 0.001-0.01). At the phylum level we observed significantly reduced Firmicutes and Deferribacterota, and elevated Bacteroidota, Verrucomicrobiota, and Proteobacteria, in pre-hypertensive SHRSP, as compared to WKY. At the genus level we identified 18 bacteria whose relative abundance was significantly different in SHRSP versus WKY at the pre-hypertensive ages of 4 or 6 weeks. In an attempt to further refine bacterial candidates that might contribute to the SHRSP phenotype, we compared the functional capacity of WKY versus SHRSP microbial communities. We identified significant differences in amino acid metabolism. Using untargeted metabolomics we found significant reductions in metabolites of the tryptophan-kynurenine pathway and increased indole metabolites in SHRSP versus WKY plasma. Overall, we provide further evidence that gut dysbiosis contributes to hypertension in the SHRSP model, and suggest for the first time the potential involvement of tryptophan metabolizing microbes.

Dataset Information

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

Publications

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

Similar Datasets

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