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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:776.)
© 2003 American Heart Association, Inc.

Vascular Biology

NAD(P)H Oxidase Mediates Angiotensin II–Induced Vascular Macrophage Infiltration and Medial Hypertrophy

Jianhua Liu; Fang Yang; Xiao-Ping Yang; Michelle Jankowski; Patrick J. Pagano

From the Hypertension and Vascular Research Division and the Biostatistics Department (M.J.), Henry Ford Hospital, Detroit, Mich.

Correspondence to Patrick J. Pagano, PhD, E & R Building, Room 7044, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202-2689. E-mail ppagano1{at}hfhs.org

Objective— Our preliminary data suggested that angiotensin II (Ang II)–induced reactive oxygen species are involved in intercellular adhesion molecule-1 (ICAM-1) expression and leukocyte infiltration in the rat thoracic aorta. Other reports demonstrating reactive oxygen species–induced cell growth suggested a potential role of NAD(P)H oxidase in vascular hypertrophy. In the present study, we postulate that NAD(P)H oxidase is functionally involved in Ang II–induced ICAM-1 expression, macrophage infiltration, and vascular growth, and that oxidase inhibition attenuates these processes independently of a reduction in blood pressure.

Methods and Results— Rats were infused subcutaneously with vehicle or Ang II (750 µg/kg per day) for 1 week in the presence or absence of gp91 docking sequence (gp91ds)-tat peptide (1 mg/kg per day), a cell-permeant inhibitor of NAD(P)H oxidase. Immunohistochemical staining for ICAM-1 and ED1, a marker of monocytes and macrophages, showed that both were markedly increased with Ang II compared with vehicle and were reduced in rats receiving Ang II plus gp91ds-tat. This effect was accompanied by an Ang II–induced increase in medial hypertrophy that was attenuated by coinfusion of gp91ds-tat; however, gp91ds-tat had no effect on blood pressure.

Conclusions— Ang II–enhanced NAD(P)H oxidase plays a role in the induction of ICAM-1 expression, leukocyte infiltration, and vascular hypertrophy, acting independently of changes in blood pressure.

Key Words: NADPH oxidoreductase • NAD(P)H oxidase • hypertrophy • inflammation • angiotensin II

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