title: Angiotensin II inhibits endothelial cell motility through an AT1-dependent oxidant-sensitive decrement of nitric oxide availability.
abstract: OBJECTIVE
  The migratory capability of vascular endothelial cells plays a pivotal role in the maintenance of vessel wall integrity and is stimulated by nitric oxide (NO). Angiotensin II increases NAD(P)H oxidase activity in endothelial cells, thereby promoting reactive oxygen species (ROS) generation. Because ROS can both reduce NO synthase activity and increase NO breakdown, thus impairing NO availability in endothelial cells, we evaluated the effect of angiotensin II on human vascular endothelial cell (HUVEC) motility.
  
  
  RESULTS
  Angiotensin II dose- and time-dependently reduced HUVEC migration. Besides inhibiting HUVEC motility, angiotensin II altered intracellular glutathione redox status. The generation of ROS by cultured HUVECs was significantly increased by angiotensin II. Furthermore, angiotensin II reduced NO metabolite concentrations in culture media. The angiotensin II type 1 receptor antagonist candesartan cilexetil attenuated the inhibitory action exerted by angiotensin II on HUVEC motility, reversed the angiotensin II-induced increase in intracellular oxidative stress, and restored NO availability. Similar effects were exerted by the flavonoid inhibitor diphenylene iodinium and the antioxidant agent N-acetyl-L-cysteine.
  
  
  CONCLUSIONS
  All together, our data demonstrate that angiotensin II inhibits HUVEC motility by reducing NO availability. Such reduction is due to an angiotensin II type 1 receptor-dependent increment in intracellular ROS generation.
authors.affiliation: Department of Internal Medicine and Public Health, University of L'Aquila, Via Vetoio, Blocco 11, 67100, Coppito, L'Aquila, Italy. giovambattista.desideri@cc.univaq.it
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Desideri
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Bravi
authors.forename: Marzia
authors.initials: M
authors.lastname: Tucci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Croce
authors.forename: Maria Contina
authors.initials: MC
authors.lastname: Marinucci
authors.forename: Anna
authors.initials: A
authors.lastname: Santucci
authors.forename: Edoardo
authors.initials: E
authors.lastname: Alesse
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferri
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D016877:Oxidants; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016877:Oxidants; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D019255:NADPH Oxidases; D005978:Glutathione; C081643:candesartan