title: Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension.
abstract: BACKGROUND
  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.
  
  
  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.affiliation: Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Marvar
authors.forename: Salim R
authors.initials: SR
authors.lastname: Thabet
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Guzik
authors.forename: Heinrich E
authors.initials: HE
authors.lastname: Lob
authors.forename: Louise A
authors.initials: LA
authors.lastname: McCann
authors.forename: Connie
authors.initials: C
authors.lastname: Weyand
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gordon
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000804:Angiotensin II; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure; D004195:Disease Models, Animal; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006830:Hydralazine / Q000008:administration & dosage; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009638:Norepinephrine; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D020542:Third Ventricle / Q000276:immunology* / Q000293:injuries / Q000503:physiopathology; D013997:Time Factors; D014657:Vasculitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D000959:Antihypertensive Agents; D018398:Homeodomain Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013481:Superoxides; D000804:Angiotensin II; C064658:RAG-1 protein; D006830:Hydralazine; D009638:Norepinephrine