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

De Ciuceis, C., Amiri, F., Brassard, P., Endemann, D.H., Touyz, R.M. and Schriffin, E.L. (2005) 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. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(10), pp. 2106-2113. (doi: 10.1161/01.ATV.0000181743.28028.57)

Abstract

<b>Objective—</b> 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.<p></p> <b>Methods and Results—</b> 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).<p></p> <b>Conclusions—</b> 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Touyz, Professor Rhian
• Authors: De Ciuceis, C., Amiri, F., Brassard, P., Endemann, D.H., Touyz, R.M., and Schriffin, E.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Arteriosclerosis, Thrombosis, and Vascular Biology
• Publisher: American Heart Association
• ISSN: 1079-5642
• ISSN (Online): 1524-4636
• Published Online: 11 August 2005