title: Hypertension-Linked Pathophysiological Alterations in the Gut.
abstract: BACKGROUND
  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.
  
  
  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.
authors: 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.
authors: Monica M
authors: MM
authors: Santisteban
authors: 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.
authors: Yanfei
authors: Y
authors: Qi
authors: 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.
authors: Jasenka
authors: J
authors: Zubcevic
authors: 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.
authors: Seungbum
authors: S
authors: Kim
authors: 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.
authors: Tao
authors: T
authors: Yang
authors: 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.
authors: Vinayak
authors: V
authors: Shenoy
authors: 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.
authors: Colleen T
authors: CT
authors: Cole-Jeffrey
authors: 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.
authors: Gilberto O
authors: GO
authors: Lobaton
authors: 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.
authors: Daniel C
authors: DC
authors: Stewart
authors: 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.
authors: Andres
authors: A
authors: Rubiano
authors: 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.
authors: Chelsey S
authors: CS
authors: Simmons
authors: 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.
authors: Fernando
authors: F
authors: Garcia-Pereira
authors: 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.
authors: Richard D
authors: RD
authors: Johnson
authors: 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.
authors: Carl J
authors: CJ
authors: Pepine
authors: 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.
authors: Mohan K
authors: MK
authors: Raizada
mesh_terms: D000804:Angiotensin II / Q000633:toxicity; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II
keywords: autonomic nervous system; gut; hypertension; inflammation; intestines; microbiota