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 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.
Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 West Grand Blvd, Detroit MI 48202-2689, USA.
Tang-Dong
TD
Liao
Xiao-Ping
XP
Yang
Yun-He
YH
Liu
Edward G
EG
Shesely
Maria A
MA
Cavasin
William A
WA
Kuziel
Patrick J
PJ
Pagano
Oscar A
OA
Carretero
D000419:Albuminuria / Q000175:diagnosis; D000804:Angiotensin II; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009400:Nephrosclerosis / Q000209:etiology* / Q000473:pathology*; D011336:Probability; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000032:analysis*; D019707:Receptors, Chemokine / Q000032:analysis*; D012016:Reference Values; D012680:Sensitivity and Specificity
D017382:Reactive Oxygen Species; D019707:Receptors, Chemokine; D000804:Angiotensin II