Document Detail


Azelnidipine has anti-atherosclerotic effects independent of its blood pressure-lowering actions in monkeys and mice.
MedLine Citation:
PMID:  17481639     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Calcium channel blockers (CCBs) have been shown to improve clinical outcomes in atherosclerotic vascular disease. The mechanisms underlying the vasculoprotective effects of a third-generation calcium channel blocker, azelnidipine, are incompletely understood. We asked whether azelnidipine attenuates atherosclerosis in monkeys and mice beyond its blood pressure-lowering effects. Cynomolgus monkeys were randomized to three groups after 4 weeks of a high cholesterol diet: control group (no treatment) and 3 and 10mg/kg daily azelnidipine; these doses have no effect on systemic arterial pressure or heart rate. Atherosclerosis was induced in the aorta by balloon injury, and the diet and treatment were continued for an additional 24 weeks. Azelnidipine did not affect blood lipid profiles, but reduced the development of atherosclerosis as detected by the elimination of local oxidative stress and reduced expression of monocyte chemoattractant protein-1 and platelet-derived growth factor. Azelnidipine also reduced the proliferation and migration of vascular smooth muscle cells in vitro. In atherosclerotic ApoE-knockout (ApoE-KO) mice fed a high cholesterol diet, azelnidipine but not amlodipine reduced the development of atherosclerosis. Neither drug changed the lipid profiles or systolic blood pressure of the mice. Thus, azelnidipine at clinically relevant doses exhibited anti-atherosclerotic effects in monkeys and mice independent of its blood pressure-lowering effects, suggesting that azelnidipine might be as a "vasculoprotective calcium channel blocker".
Authors:
Kaku Nakano; Kensuke Egashira; Kisho Ohtani; Zhao Gang; Eiko Iwata; Miho Miyagawa; Kenji Sunagawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-03
Journal Detail:
Title:  Atherosclerosis     Volume:  196     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-14     Completed Date:  2008-02-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  172-9     Citation Subset:  IM    
Affiliation:
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Thoracic / drug effects*,  pathology
Atherosclerosis / drug therapy*,  pathology
Azetidinecarboxylic Acid / analogs & derivatives*,  pharmacology
Blood Pressure / drug effects
Calcium Channel Blockers / pharmacology*
Chemokine CCL2 / drug effects
Dihydropyridines / pharmacology*
Disease Models, Animal
Dose-Response Relationship, Drug
Macaca fascicularis
Male
Mice
Mice, Knockout
Platelet-Derived Growth Factor / drug effects
Random Allocation
Tunica Intima / drug effects*,  pathology
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Chemokine CCL2; 0/Dihydropyridines; 0/Platelet-Derived Growth Factor; 123524-52-7/azelnidipine; 2517-04-6/Azetidinecarboxylic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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