title: Vascular smooth muscle Jak2 mediates angiotensin II-induced hypertension via increased levels of reactive oxygen species.
abstract: OBJECTIVE
  Angiotensin II (Ang II) type AT(1) receptors expressed on vascular smooth muscle cells (VSMCs) couple to the Jak2 signalling pathway. However, the importance of this tissue-specific coupling is poorly understood. The purpose of this investigation was to determine the importance of VSMC-derived Jak2 in angiotensin II-mediated hypertension.
  
  
  RESULTS
  The Cre-loxP system was used to conditionally eliminate Jak2 tyrosine kinase expression within the smooth muscle cells of mice. Following chronic Ang II infusion, the resulting increase in mean arterial pressure (MAP) was significantly attenuated in the Jak2 null mice when compared with littermate controls. The VSMC Jak2 null mice were also protected from the Ang II-induced vascular remodelling. Aortic rings from the VSMC Jak2 null mice exhibited reduced Ang II-induced contraction and enhanced endothelial-dependent relaxation via increased nitric oxide (NO) bioavailability. When compared with controls, the VSMC Jak2 nulls also had lower levels of hydrogen peroxide, Rho kinase activity, and intracellular Ca(2+) in response to Ang II.
  
  
  CONCLUSIONS
  The data indicate that VSMC Jak2 expression is involved in the pathogenesis of Ang II-dependent hypertension due to the increased presence of reactive oxygen species (ROS). As such, VSMC-derived Jak2 tyrosine kinase modulates overall vascular tone via multiple, non-redundant mechanisms.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Annet
authors.initials: A
authors.lastname: Kirabo
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Kearns
authors.forename: Yagna P
authors.initials: YP
authors.lastname: Jarajapu
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Sasser
authors.forename: Suk Paul
authors.initials: SP
authors.lastname: Oh
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
authors.forename: Hideko
authors.initials: H
authors.lastname: Kasahara
authors.forename: Arturo J
authors.initials: AJ
authors.lastname: Cardounel
authors.forename: Chris
authors.initials: C
authors.lastname: Baylis
authors.forename: Kay-Uwe
authors.initials: KU
authors.lastname: Wagner
authors.forename: Peter P
authors.initials: PP
authors.lastname: Sayeski
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000503:physiopathology; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D053614:Janus Kinase 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D054460:rho-Associated Kinases; D002118:Calcium