title: Carvedilol reduces the severity of atherosclerosis in apolipoprotein E-deficient mice via reducing superoxide production.
abstract: It has been shown that oxidative stress may play an important role in the development of atherosclerosis, and carvedilol has the capacity of reducing oxidative stress. Accordingly, we assessed the hypothesis that carvedilol may reduce the severity of atherosclerosis in apolipoprotein E (apoE)-deficient mice in addition to its hemodynamic effects. Atherosclerosis was induced in apoE-deficient mice fed a high-fat diet containing 0.3% cholesterol. Mice were orally treated with propranolol (30 mg/kg/day), metoprolol (75 mg/kg/day) and carvedilol (10 mg/kg/day) over eight weeks (each group n = 7-9). Fatty streak plaque developed in apoE-deficient mice, and was suppressed in mice treated with all three drugs. The accumulation of macrophages and expression of CD4(+) and CD8(+) cells in the lesions were decreased by the treatment of the drugs, of which carvedilol was the most effective. In addition, carvedilol reduced superoxide production in aortic walls detected by ethidium staining. There were no significant changes in blood pressure among the study groups. The heart rates in the treated groups were decreased by 4%-12% compared with the control group, with carvedilol yielding the highest suppression of heart rate. The β-blocker treatment did not significantly modify the serum lipid profiles. Carvedilol may suppress atherosclerosis via reducing superoxide production, in addition to the hemodynamic modifications in this animal model.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Shimada
authors.forename: Emi
authors.initials: E
authors.lastname: Hirano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Fujita
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kishimoto
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005609:Free Radicals / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D001057:Apolipoproteins E; D002227:Carbazoles; D002791:Cholesterol, Dietary; D005609:Free Radicals; D008055:Lipids; D011412:Propanolamines; D000077261:Carvedilol; D013481:Superoxides; D011433:Propranolol; D008790:Metoprolol