CC chemokine receptor 2 is required for macrophage infiltration and vascular hypertrophy in angiotensin II-induced hypertension

Recent studies have identified the presence of macrophages in the arterial wall of hypertensive animals and suggested that as is the case in atheroscl erosis, macrophage products may be important mediators of the adaptive resp onse of the arterial wall. In support of this, we have previously shown tha t the expression of monocyte chemoattractant protein-1 is upregulated in th e arteries of hypertensive animals. We hypothesized that macrophage recruit ment is a critical step in the pathogenesis of hypertension. To obtain insi ghts into this potential mechanism, we made use of mice deficient in the CC chemokine receptor 2 (CCR2), the receptor for monocyte chemoattractant pro tein-1. Hypertension was induced with the subcutaneous administration of an giotensin II (0.75 mg . kg(-1) . d(-1)) for 7 days. Using in situ hybridiza tion with a probe for c-fms to identify macrophages, we found that hyperten sion-induced macrophage infiltration of the arterial wall was virtually eli minated in CCR2-deficient mice. In addition, vascular hypertrophy was reduc ed by approximate to 65% compared with wild-type animals. These data demons trate that CCR2 is essential for the recruitment of macrophages into the ar terial wall in the setting of hypertension. Furthermore, the decreased hype rtrophic response suggests that vascular hypertrophy occurs in part as a co nsequence of macrophage infiltration. In angiotensin II-induced hypertensio n, CCR2-mediated responses are critical to the process of macrophage recrui tment and vascular hypertrophy and may represent one mechanism by which at least some forms of hypertension may lead to the development of atheroscler osis.