Calcium antagonists prevent monocyte and endothelial cell-induced modification of low density lipoproteins.
Low density lipoprotein (LDL) incubated in the presence of the calcium antagonists verapamil, nifedipine and flunarizine were more resistant than control LDL to human monocyte- or endothelial cell-induced modification, as assessed by electrophoretic mobility in agarose gel, thiobarbituric acid reactive substance content, and degradation by J774 macrophages. The efficiency of the drugs was: flunarizine greater than nifedipine greater than verapamil. Moreover, a 24 h preculture with calcium antagonists significantly impaired the ability of cells to modify LDL in the absence of the drugs. All the studied drugs also inhibited copper-induced autooxidation of LDL. None of the studied calcium antagonists, at concentrations up to 10(-4) M, significantly reacted with free radicals as assessed by the 1,1-diphenyl-2-picrylhydrazyl test. It is suggested that such a protective effect of calcium antagonists against LDL peroxidation could play a role in the previously reported antiatherogenic effect of these drugs.
Breugnot
C
C
Institut de Recherches Servier (IDRS), Suresnes, France.
Mazière
C
C
Auclair
M
M
Mora
L
L
Ronveaux
M F
MF
Salmon
S
S
Santus
R
R
Morlière
P
P
Lenaers
A
A
Mazière
J C
JC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D003864:Depression, Chemical; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers; D006801:Humans; D007231:Infant, Newborn; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D014810:Vitamin E / Q000494:pharmacology
D002121:Calcium Channel Blockers; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D014810:Vitamin E; D002118:Calcium