Hypertension-Linked Pathophysiological Alterations in the Gut
Open accessAbstract
Rationale: Sympathetic nervous system control of inflammation plays a central role in hypertension. The gut receives significant sympathetic innervation, is densely populated with a diverse microbial ecosystem, and contains immune cells that greatly impact overall inflammatory homeostasis. Despite this uniqueness, little is known about the involvement of the gut in hypertension. Objective: Test the hypothesis that increased sympathetic drive to the gut is associated with increased gut wall permeability, increased inflammatory status, and microbial dysbiosis and that these gut pathological changes are linked to hypertension. Methods and Results: Gut epithelial integrity and wall pathology were examined in spontaneously hypertensive rat and chronic angiotensin II infusion rat models. The increase in blood pressure in spontaneously hypertensive rat was associated with gut pathology that included increased intestinal permeability and decreased tight junction proteins. These changes in gut pathology in hypertension were associated with alterations in microbial communities relevant in blood pressure control. We also observed enhanced gut–neuronal communication in hypertension originating from paraventricular nucleus of the hypothalamus and presenting as increased sympathetic drive to the gut. Finally, angiotensin-converting enzyme inhibition (captopril) normalized blood pressure and was associated with reversal of gut pathology. Conclusions: A dysfunctional sympathetic–gut communication is associated with gut pathology, dysbiosis, and inflammation and plays a key role in hypertension. Thus, targeting of gut microbiota by innovative probiotics, antibiotics, and fecal transplant, in combination with the current pharmacotherapy, may be a novel strategy for hypertension treatment.
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In spontaneously hypertensive rats, blood pressure reduction as a result of ACE inhibition had beneficial effects on gut pathology, including reductions in mucosal permeability, inflammation, and dysbiosis.
“In SHRs, BP reduction as a result of ACE inhibition had beneficial effects on gut pathology (for example, reductions in mucosal permeability, inflammation and dysbiosis)105.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [105]
Prehypertensive juvenile SHRs had reduced levels of multiple tight junction proteins but similar gut permeability compared with juvenile WKY rats.
“Although these changes were more profound in adult SHRs than in juvenile SHRs that had not yet developed hypertension, the prehypertensive juvenile SHRs had reduced levels of multiple tight junction proteins but similar gut permeability compared with juvenile WKY rats91.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [91]
Spontaneously hypertensive rats (SHRs) showed pathophysiological changes in the gut, including decreased numbers of goblet cells and villi length and increased fibrosis compared with age-matched normotensive Wistar Kyoto (WKY) controls.
“Moreover, spontaneously hypertensive rats (SHRs) showed patho-physiological changes in the gut, including decreased numbers of goblet cells and villi length and increased fibrosis compared with age-matched normotensive Wistar Kyoto (WKY) controls91.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [91]
Our research group was the first to demonstrate a contribution of the brain-gut-bone-marrow axis to blood pressure elevation.
“Our research group was the first to demonstrate a contribution of the brain-gut-bone-marrow axis to blood pressure elevation15,87,91,154–159.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [91]
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- Authors
- Santisteban, M. M., Qi, Y., Zubcevic, J., Kim, S., Yang, T., Shenoy, V., Cole-Jeffrey, C. T., Lobaton, G. O., Stewart, D. C., Rubiano, A., Simmons, C. S., Garcia-Pereira, F., Johnson, R. D., Pepine, C. J., & Raizada, M. K.
- Affiliations
- University of Florida (US)
- From the Department of Physiology and Functional Genomics, College of Medicine (M.M.S., S.K., C.T.C.-J., G.O.L., M.K.R.), Division of Cardiovascular Medicine, Department of Medicine (Y.Q., C.S.S., C.J.P.), Department of Physiological Sciences, College of Veterinary Medicine (J.Z., T.Y., F.G.-P., R.D.J.), Department of Pharmacodynamics, College of Pharmacy (V.S.), J. Crayton Pruitt Family Department of Biomedical Engineering (D.C.S., C.S.S.); Mechanical and Aerospace Engineering, Herbert Wertheim...
- Corresponding author
- Santisteban, Monica M.
- Qi, Yanfei
- ORCID
- Venue
- Circulation Research
- Published
- 2017-01-20
- Volume
- 120
- Issue
- 2
- Pages
- 312-323
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC5250568
- OpenAlex
- W2543448041
- Cited by
- 525
- References
- 62
- Citations by year
- 2026: 34 · 2025: 57 · 2024: 62 · 2023: 67 · 2022: 60 · 2021: 79 · 2020: 62 · 2019: 45 · 2018: 34 · 2017: 23 · 2016: 2
- FWCI
- 18.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL033610, R37HL033610, R01HL132448)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- hypertension, gut-brain axis, sympathetic nervous system, intestinal permeability, tight junction proteins, intestinal epithelial integrity, gut dysbiosis, intestinal inflammation, paraventricular nucleus, angiotensin II, captopril, angiotensin-converting enzyme inhibition, spontaneously hypertensive rats, fecal microbiota transplantation, probiotics
- MeSH terms
- Gastrointestinal Microbiome, Angiotensin II, Angiotensin-Converting Enzyme Inhibitors, Animals, Hypertension, Intestinal Mucosa, Male, Permeability, Rats, Inbred SHR, Rats, Inbred WKY, Rats, Sprague-Dawley, Rats, Wistar, Rats
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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