Role of Inflammation in the Development of Renal Damage and Dysfunction in Angiotensin II–Induced Hypertension

Angiotensin II (Ang II)–induced hypertension is associated with an inflammatory response that may contribute to the development of target organ damage. We tested the hypothesis that, in Ang II–induced hypertension, CC chemokine receptor 2 (CCR2) activation plays an important role in the development...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2008-08, Vol.52 (2), p.256-263
Main Authors: Liao, Tang-Dong, Yang, Xiao-Ping, Liu, Yun-He, Shesely, Edward G, Cavasin, Maria A, Kuziel, William A, Pagano, Patrick J, Carretero, Oscar A
Format: Article
Language:English
Subjects:
Albuminuria - diagnosis
Angiotensin II
Animals
Blotting, Western
Cell Movement
Cell Proliferation
Disease Models, Animal
Glomerular Filtration Rate
Hypertension - chemically induced
Hypertension - complications
Hypertension - physiopathology
Immunohistochemistry
Inflammation - physiopathology
Macrophages - cytology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nephrosclerosis - etiology
Nephrosclerosis - pathology
Probability
Random Allocation
Reactive Oxygen Species - analysis
Receptors, Chemokine - analysis
Reference Values
Sensitivity and Specificity
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Summary:Angiotensin II (Ang II)–induced hypertension is associated with an inflammatory response that may contribute to the development of target organ damage. We tested the hypothesis that, in Ang II–induced hypertension, CC chemokine receptor 2 (CCR2) activation plays an important role in the development of renal fibrosis, damage, and dysfunction by causing oxidative stress, macrophage infiltration, and cell proliferation. To test this hypothesis, we used CCR2 knockout mice (CCR2). The natural ligand of CCR2 is monocyte chemoattractant protein-1, a chemokine important for macrophage recruitment and activation. CCR2 and age-matched wild-type (CCR2) C57BL/6J mice were infused continuously with either Ang II (5.2 ng/10 g per minute) or vehicle via osmotic minipumps for 2 or 4 weeks. Ang II infusion caused similar increases in systolic blood pressure and left ventricular hypertrophy in both strains of mice. However, in CCR2 mice with Ang II–induced hypertension, oxidative stress, macrophage infiltration, albuminuria, and renal damage were significantly decreased, and glomerular filtration rate was significantly higher than in CCR2 mice. We concluded that, in Ang II–induced hypertension, CCR2 activation plays an important role in the development of hypertensive nephropathy via increased oxidative stress and inflammation.
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.108.112706