Oxidative stress in mononuclear cells plays a dominant role in their adhesion to mouse femoral artery after injury.
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.
Hagita
Sumihiko
S
Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
Osaka
Mizuko
M
Shimokado
Kentaro
K
Yoshida
Masayuki
M
D000098:Acetophenones / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001167:Arteritis / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D005263:Femoral Artery / Q000293:injuries* / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology; D016023:Integrins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D000098:Acetophenones; D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D007093:Imidazoles; D016023:Integrins; D013777:Tetrazoles; C437965:olmesartan; C056165:acetovanillone