Format

Send to

Choose Destination
Circ Res. 2017 Jan 20;120(2):312-323. doi: 10.1161/CIRCRESAHA.116.309006. Epub 2016 Oct 31.

Hypertension-Linked Pathophysiological Alterations in the Gut.

Author information

1
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 College of Engineering (A.R., C.S.S.), University of Florida, Gainesville.
2
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 College of Engineering (A.R., C.S.S.), University of Florida, Gainesville. yanfeiqi@ufl.edu mraizada@ufl.edu.

Abstract

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.

KEYWORDS:

autonomic nervous system; gut; hypertension; inflammation; intestines; microbiota

PMID:
27799253
PMCID:
PMC5250568
DOI:
10.1161/CIRCRESAHA.116.309006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center