Document Detail


Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension.
MedLine Citation:
PMID:  20558826     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: We have previously found that T lymphocytes are essential for development of angiotensin II-induced hypertension; however, the mechanisms responsible for T-cell activation in hypertension remain undefined.
OBJECTIVE: We sought to study the roles of the CNS and pressure elevation in T-cell activation and vascular inflammation caused by angiotensin II.
METHODS AND RESULTS: To prevent the central actions of angiotensin II, we created anteroventral third cerebral ventricle (AV3V) lesions in mice. The elevation in blood pressure in response to angiotensin II was virtually eliminated by AV3V lesions, as was activation of circulating T cells and the vascular infiltration of leukocytes. In contrast, AV3V lesioning did not prevent the hypertension and T-cell activation caused by the peripheral acting agonist norepinephrine. To determine whether T-cell activation and vascular inflammation are attributable to central influences or are mediated by blood pressure elevation, we administered hydralazine (250 mg/L) in the drinking water. Hydralazine prevented the hypertension and abrogated the increase in circulating activated T cells and vascular infiltration of leukocytes caused by angiotensin II.
CONCLUSIONS: We conclude that the central and pressor effects of angiotensin II are critical for T-cell activation and development of vascular inflammation. These findings also support a feed-forward mechanism in which modest degrees of blood pressure elevation lead to T-cell activation, which in turn promotes inflammation and further raises blood pressure, leading to severe hypertension.
Authors:
Paul J Marvar; Salim R Thabet; Tomasz J Guzik; Heinrich E Lob; Louise A McCann; Connie Weyand; Frank J Gordon; David G Harrison
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-06-17
Journal Detail:
Title:  Circulation research     Volume:  107     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-23     Completed Date:  2010-08-24     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  263-70     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adoptive Transfer
Angiotensin II
Animals
Antihypertensive Agents / administration & dosage
Blood Pressure
Disease Models, Animal
Genes, T-Cell Receptor alpha
Genes, T-Cell Receptor beta
Homeodomain Proteins / genetics,  metabolism
Hydralazine / administration & dosage
Hypertension / chemically induced,  genetics,  immunology*,  metabolism,  physiopathology,  prevention & control
Lymphocyte Activation* / drug effects
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Norepinephrine
Receptors, Antigen, T-Cell, alpha-beta / immunology
Superoxides / metabolism
T-Lymphocytes / drug effects,  immunology*,  transplantation
Third Ventricle / immunology*,  injuries,  physiopathology
Time Factors
Vasculitis / chemically induced,  genetics,  immunology*,  metabolism,  physiopathology,  prevention & control
Grant Support
ID/Acronym/Agency:
EY11916/EY/NEI NIH HHS; HL390006/HL/NHLBI NIH HHS; HL58000/HL/NHLBI NIH HHS; HL59248/HL/NHLBI NIH HHS; HL63919/HL/NHLBI NIH HHS; P01 HL058000-01A10002/HL/NHLBI NIH HHS; P01 HL058000-11A1/HL/NHLBI NIH HHS; R01 HL039006-23/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Homeodomain Proteins; 0/Receptors, Antigen, T-Cell, alpha-beta; 11062-77-4/Superoxides; 11128-99-7/Angiotensin II; 128559-51-3/RAG-1 protein; 51-41-2/Norepinephrine; 86-54-4/Hydralazine
Comments/Corrections
Comment In:
Circ Res. 2010 Jul 23;107(2):166-7   [PMID:  20651292 ]

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