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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.

journal_name

Vascul Pharmacol

journal_title

Vascular pharmacology

authors

Takayama M,Matsubara M,Arakawa E,Takada C,Ina Y,Hasegawa K,Yao K

doi

10.1016/j.vph.2006.11.004

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

302-8

issue

4

eissn

1537-1891

issn

1879-3649

pii

S1537-1891(06)00682-3

journal_volume

46

pub_type

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