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(Hypertension. 2008;51:797.)
© 2008 American Heart Association, Inc.

Original Articles

Oxidative Stress in Mononuclear Cells Plays a Dominant Role in Their Adhesion to Mouse Femoral Artery After Injury

From the Life Science and Bioethics Research Center (S.H., M.O., M.Y.) and Department of Geriatrics and Vascular Medicine, Graduate School of Medicine (S.H., K.S.), Tokyo Medical and Dental University, Tokyo, Japan.

Correspondence Masayuki Yoshida, Life Science and Bioethics Research Center, Tokyo Medical and Dental University, 1-5-45 Yushima Building D-809, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail masavasc{at}tmd.ac.jp

Leukocyte recruitment plays a pivotal role during inflammation after vascular injury. The importance of oxidative stress in vascular injury and its modulation by angiotensin II receptor blockers (olmesartan) have been demonstrated. We examined the contribution of leukocyte-associated oxidative stress in acute-phase leukocyte recruitment and its modulation by olmesartan. Male mice were treated with olmesartan (5 mg/kg per day) or vehicle for 7 days before the transluminal wire injury of the femoral artery. Intravital microscopy of the artery revealed that the mechanical injury increased adherent leukocytes at both 24 hours and 7 days after the injury, which was significantly reduced by olmesartan treatment. Dihydroethidium-associated fluorescence intensity observed in vehicle-treated mice was significantly diminished under olmesartan treatment. Apocynin, a nicotinamide-adenine dinucleotide phosphate oxidase inhibitor, showed a similar inhibitory effect on the leukocyte adhesion. Adoptive transfer of mononuclear cells, harvested from mice after wire injury, but not from those without wire injury, exhibited adhesion to the recipient injured artery. Furthermore, olmesartan treatment of mononuclear cells, but not of injured vasculature, reduced their recruitment to the injured artery. These data indicate that leukocyte recruitment to the mechanically injured artery is mediated by oxidative stress in leukocytes but not in vasculatures. Treatment with olmesartan blocked leukocyte recruitment by antagonizing mononuclear cells-associated oxidative stress.

Key Words: angiotensin receptors • imaging • inflammation • oxidant stress • leukocytes

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