Published Online
on June 9, 2008

A more recent version of this article appeared on August 1, 2008

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Submitted on February 27, 2008
Revised on March 24, 2008

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

Tang-Dong Liao; Xiao-Ping Yang; Yun-He Liu; Edward G. Shesely; Maria A. Cavasin; William A. Kuziel; Patrick J. Pagano; and Oscar A. Carretero^*

From the Hypertension and Vascular Research Division (T.-D.L., X.-P.Y., Y.-H.L., E.G.S., M.A.C., P.J.P., O.A.C.), Department of Internal Medicine, Henry Ford Hospital, Detroit, Mich; and PDL BioPharma, Inc (W.A.K.), Fremont, Calif.

^* To whom correspondence should be addressed. E-mail: ocarret1{at}hfhs.org.

Abstract—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.

Key words: inflammation • chemokine receptors • macrophage • reactive oxygen species • kidney diseases • albuminuria • fibrosis

Related Article:

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