title: Combination of amlodipine and atorvastatin synergistically reduces leukocyte recruitment to mechanically injured mouse femoral artery.
abstract: Recent studies have demonstrated a potential synergistic effect of the combination of amlodipine with atorvastatin to reduce acute inflammation. The intraluminal wire injury of the mouse femoral artery induced significant leukocyte recruitment to the injured area and oxidative stress within 24 h. Administration of low-dose amlodipine (0.5 mg kg(-1) per day) or atorvastatin (1 mg kg(-1) per day) alone for 7 days failed to modulate leukocyte adhesion, whereas their co-administration for 7 days significantly inhibited leukocyte adhesion. Moreover, flow cytometric analysis showed that injury-induced oxidative stress and CD11b expression in three leukocyte fractions were elevated after injury and then reduced after the co-administration. Next, adoptive transfer of mononuclear cells (MNCs) was performed and MNCs were harvested from mice after wire injury exhibited adhesion to the recipient injured artery. Furthermore, the co-administration of low-dose atorvastatin and amlodipine to MNCs or the vasculature reduced the recruitment of MNCs to the injured artery. Our findings indicate that amlodipine and atorvastatin synergistically inhibit vascular inflammation. The underlying mechanisms of their effect involve, at least in part, stabilizing oxidative stress at the point of injury, suggesting the clinical efficacy of this drug combination for the treatment of vascular diseases.
authors.affiliation: Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Sumihiko
authors.initials: S
authors.lastname: Hagita
authors.forename: Mizuko
authors.initials: M
authors.lastname: Osaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shimokado
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D019264:Adoptive Transfer; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000069059:Atorvastatin; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005263:Femoral Artery / Q000293:injuries* / Q000473:pathology; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000637:transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D017311:Amlodipine; D000069059:Atorvastatin; D019255:NADPH Oxidases