title: Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of angiotensin II-infused macrophage colony-stimulating factor-deficient mice: evidence for a role in inflammation in angiotensin-induced vascular injury.
abstract: OBJECTIVE
  Angiotensin (Ang) II-induced vascular damage may be partially mediated by reactive oxygen species generation and inflammation. Homozygous osteopetrotic mice (Op/Op), deficient in macrophage colony-stimulating factor (m-CSF), exhibit reduced inflammation. We therefore investigated Ang II effects on vascular structure, function, and oxidant stress generation in this model.
  
  
  RESULTS
  Adult Op/Op, heterozygous (Op/+), and wild type (+/+) mice underwent 14-day Ang II (1000 ng/kg per minute) or saline infusion. Blood pressure (BP) was assessed by radiotelemetry, mesenteric resistance artery vascular reactivity was studied on a pressurized myograph, and vascular superoxide and NAD(P)H oxidase activity by lucigenin chemiluminescence. Ang II increased BP in Op/+ and +/+ mice but not in Op/Op. Ang II-treated Op/+ and +/+ mice showed reduced acetylcholine-mediated relaxation (maximal relaxation, respectively, 64% and 67% versus 84% and 93% in respective controls; P<0.05), which was unaffected by L-NAME. Ang II-infused Op/Op mice arteries showed significantly less endothelial dysfunction than vehicle-infused counterparts (maximal relaxation 87% versus 96% in shams). Resistance arteries from Ang II-infused +/+ and Op/+ mice had significantly increased media-to-lumen ratio and media thickness, neither of which was altered in Op/Op mice compared with untreated littermates. Vascular media cross-sectional area, NAD(P)H oxidase activity and expression, and vascular cell adhesion molecule (VCAM)-1 expression were significantly increased by Ang II only in +/+ mice (P<0.05).
  
  
  CONCLUSIONS
  m-CSF-deficient mice (Op/Op) developed less endothelial dysfunction, vascular remodeling, and oxidative stress induced by Ang II than +/+ littermates, suggesting a critical role of m-CSF and proinflammatory mediators in Ang II-induced vascular injury.
authors.affiliation: CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Carolina
authors.initials: C
authors.lastname: De Ciuceis
authors.forename: Farhad
authors.initials: F
authors.lastname: Amiri
authors.forename: Pascal
authors.initials: P
authors.lastname: Brassard
authors.forename: Dierk H
authors.initials: DH
authors.lastname: Endemann
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
authors.forename: Ernesto L
authors.initials: EL
authors.lastname: Schiffrin
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008638:Mesenteric Arteries / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D019255:NADPH Oxidases / Q000378:metabolism; D010022:Osteopetrosis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D014655:Vascular Resistance; D014657:Vasculitis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D016173:Macrophage Colony-Stimulating Factor; D019255:NADPH Oxidases