title: NAD(P)H oxidase mediates angiotensin II-induced vascular macrophage infiltration and medial hypertrophy.
abstract: OBJECTIVE
  Our preliminary data suggested that angiotensin II (Ang II)-induced reactive oxygen species are involved in intercellular adhesion molecule-1 (ICAM-1) expression and leukocyte infiltration in the rat thoracic aorta. Other reports demonstrating reactive oxygen species-induced cell growth suggested a potential role of NAD(P)H oxidase in vascular hypertrophy. In the present study, we postulate that NAD(P)H oxidase is functionally involved in Ang II-induced ICAM-1 expression, macrophage infiltration, and vascular growth, and that oxidase inhibition attenuates these processes independently of a reduction in blood pressure.
  
  
  RESULTS
  Rats were infused subcutaneously with vehicle or Ang II (750 microg/kg per day) for 1 week in the presence or absence of gp91 docking sequence (gp91ds)-tat peptide (1 mg/kg per day), a cell-permeant inhibitor of NAD(P)H oxidase. Immunohistochemical staining for ICAM-1 and ED1, a marker of monocytes and macrophages, showed that both were markedly increased with Ang II compared with vehicle and were reduced in rats receiving Ang II plus gp91ds-tat. This effect was accompanied by an Ang II-induced increase in medial hypertrophy that was attenuated by coinfusion of gp91ds-tat; however, gp91ds-tat had no effect on blood pressure.
  
  
  CONCLUSIONS
  Ang II-enhanced NAD(P)H oxidase plays a role in the induction of ICAM-1 expression, leukocyte infiltration, and vascular hypertrophy, acting independently of changes in blood pressure.
authors.affiliation: Hypertension and Vascular Research Division and the Biostatistics Department, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, Mich 48202-2689, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yang
authors.forename: Michelle
authors.initials: M
authors.lastname: Jankowski
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Pagano
mesh_terms: D000447:Aldehydes / Q000032:analysis; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006023:Glycoproteins / Q000494:pharmacology*; D006984:Hypertrophy; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016037:Single-Blind Method; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology*; D014657:Vasculitis / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000447:Aldehydes; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C473031:gp91ds-tat protein, chimeric; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C027576:4-hydroxy-2-nonenal