The calcium-channel blocker lacidipine reduces the development of atherosclerotic lesions in the apoE-deficient mouse.
BACKGROUND
Lacidipine is a widely used calcium-channel blocker, which has both long-lasting antihypertensive activity and also antioxidant properties. Previous studies have demonstrated the ability of lacidipine to reduce the development of atherosclerotic lesions in several animal models.


OBJECTIVE
The present study investigated the antiatherosclerotic potential of lacidipine in the apoE-deficient mouse, an experimental model of atherosclerosis showing progressively complex and widespread lesions which closely resemble the inflammatory-fibrous plaques seen in humans.


METHODS
Lacidipine was administered daily by gavage for 10 weeks at dose levels of 0 (control), 0.3, 1.0 and 3.0 mg/kg.


RESULTS
Lacidipine administration reduces the extension of atherosclerotic lesions in the aorta of the apoE-deficient mouse without affecting plasma lipid levels. We also show that apoE-deficient mice have four-fold higher values of the proatherogenic peptide, endothelin, compared with the wild-type C57BL/6 mouse and that lacidipine administration reduced, in a dose-dependent manner, the concentrations of plasma endothelin.


CONCLUSIONS
Lacidipine has anti-atherogenic effects in the apoE-deficient mouse, and reduces plasma endothelin concentrations.
Cristofori
P
P
Department of Mecicines Safety Evaluation, GlaxoWellcome S.p.A, Mecicines Research Centre, Verona, Italy. pgc2428@glaxowellcome.uk.co
Lanzoni
A
A
Quartaroli
M
M
Pastorino
A M
AM
Zancanaro
C
C
Cominacini
L
L
Gaviraghi
G
G
Turton
J
J
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D004095:Dihydropyridines / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000097:blood; D005260:Female; D051379:Mice
D000959:Antihypertensive Agents; D001057:Apolipoproteins E; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D016232:Endothelins; C060285:lacidipine; D002784:Cholesterol