title: Comparison of the antiatherosclerotic effects of dihydropyridine calcium channel blocker and HMG-CoA reductase inhibitor on hypercholesterolemic rabbits.
abstract: The antiatherosclerotic effects of the dihydropyridine-type calcium channel blocker, benidipine hydrochloride (benidipine), and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin sodium (pravastatin), were compared in hypercholesterolemic rabbits. Male, New Zealand white rabbits were fed a 0.5% cholesterol diet. Pravastatin (10 mg/kg) or benidipine (10 mg/kg) was orally administered once daily after start of feeding. After 8 weeks of cholesterol feeding, serum cholesterol was increased and endothelial function of thoracic aorta was impaired. Pravastatin prevented elevation of serum cholesterol and aortic tunica intima hyperplasia. Although benidipine had little effect on serum cholesterol, it significantly inhibited aortic tunica intima hyperplasia and impairment of endothelial function. Expression levels of the vascular cell adhesion molecule-1 (VCAM-1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mRNA in aorta of hypercholesterolemic rabbit were higher than those of normal rabbit. Benidipine significantly prevented upregulation of VCAM-1 mRNA expression and showed a tendency to inhibit elevation of LOX-1 mRNA expression. Pravastatin significantly prevented upregulation of both VCAM-1 and LOX-1 mRNA expression. The results demonstrate that pravastatin inhibits increase of serum cholesterol and vascular dysfunction in hypercholesterolemic rabbit. Benidipine is effective in preventing vascular hyperplasia without altering serum cholesterol levels and this may be due to inhibition of expression of VCAM-1.
authors.affiliation: Department of Pharmacology and Molecular Biology, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka-ken, 411-8731, Japan. makoto.takayama@kyowa.co.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Takayama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsubara
authors.forename: Emi
authors.initials: E
authors.lastname: Arakawa
authors.forename: Chie
authors.initials: C
authors.lastname: Takada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ina
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Kozo
authors.initials: K
authors.lastname: Yao
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051127:Scavenger Receptors, Class E; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; D019010:Vascular Cell Adhesion Molecule-1; C061004:benidipine; D002784:Cholesterol; D017035:Pravastatin