Effects of the calcium channel blocker amlodipine on serum and aortic cholesterol, lipid peroxidation, antioxidant status and aortic histology in cholesterol-fed rabbits.
Reactive oxygen metabolites and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of atherosclerosis. Amlodipine, a unique third-generation dihydropyridine-type calcium channel blocker, seems to exert atheroprotective effects through its antioxidant properties related to its chemical structure and independent of its calcium channel-blocking effect. In this study, the interactions of amlodipine with major cellular antioxidants were investigated in order to elucidate the mechanisms underlying its atheroprotective effects. New Zealand white male rabbits were fed regular chow (group 1), chow with 1% cholesterol (group 2), regular chow plus 5 mg/kg/day amlodipine per os (group 3) and 1% cholesterol plus amlodipine (group 4) for 8 weeks. Total cholesterol, malondialdehyde (MDA) and vitamin E concentrations and catalase and superoxide dismutase (SOD) activities were determined in blood drawn before and after the experimental period. Aortic tissue was examined for atherosclerotic changes and aortic total cholesterol, MDA, catalase and SOD were determined. At the end of the 8-week treatment period, serum total cholesterol and plasma MDA were elevated in groups 2 and 4. In group 2, serum vitamin E and plasma SOD diminished (p < 0.05) and catalase increased (p < 0.05). In group 4, SOD activity increased at the end of treatment. MDA levels were lower and plasma SOD activities were higher in group 4 than in group 2. Aortic tissue investigations revealed higher total cholesterol and MDA concentrations and catalase activities in group 2 than in group 4, and the highest tissue SOD activity was recorded in group 4 (p < 0.05 for all comparisons). Morphological examination of aortic tissues exhibited endothelial disarrangement and lipid deposition in group 2. Histopathological alterations related to atherogenesis were less in group 4 than in group 2. Amlodipine seems to exert atheroprotective effects by reducing aortic cholesterol accumulation and blood and aortic lipid peroxidation, enhancing SOD activity both in blood and aortic tissue and suppressing the consumption of vitamin E. On the other hand, the suppression of catalase activity in blood and the aorta interferes with the drug's well-known antioxidant effects.
Turgan
Nevbahar
N
Department of Clinical Biochemistry, Ege University School of Medicine, Izmir, Turkey. turgan@med.ege.edu.tr
Habif
Sara
S
Kabaroğlu
Ceyda Gülter
CG
Mutaf
Işil
I
Ozmen
Dilek
D
Bayindir
Oya
O
Uysal
Ayşegül
A
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000032:analysis; D001011:Aorta / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002374:Catalase / Q000097:blood; D002784:Cholesterol / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D013482:Superoxide Dismutase / Q000097:blood; D014810:Vitamin E / Q000097:blood
D000975:Antioxidants; D002121:Calcium Channel Blockers; D014810:Vitamin E; D017311:Amlodipine; D002784:Cholesterol; D002374:Catalase; D013482:Superoxide Dismutase