[Effect of efonidipine hydrochloride (NZ-105) on modification of low density lipoprotein induced by rat cultured endothelial cells].
We studied the effects of efonidipine hydrochloride [NZ-105: (+/-)-2-[benzyl (phenyl) amino] ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2- yl)-4-(3-nitro-phenyl)-3-pyridinecarboxylate hydrochloride ethanol] and nisoldipine on endothelial cell-induced low density lipoprotein (LDL) modification. The modification of LDL by cultured rat endothelial cells was performed by incubating 3 micrograms protein/well LDL with 5 microM CuSO4 for 24 hr at 37 degrees C in the presence of confluent cells. The extent of modification was assayed by measuring the thiobarbituric acid-reactive substances (TBARS). Efonidipine hydrochloride reduced the TBARS level in a dose-dependent manner. At 3 x 10(-7) M, efonidipine hydrochloride showed a significant effect. On the other hand, the significant effect of nisoldipine was observed only at 10(-5) M. Thus the action of efonidipine hydrochloride on the inhibition of LDL-modification was much more potent than that of nisoldipine. As the modification of LDL was thought to play a key role in the initiation and progression of atherosclerosis, efonidipine hydrochloride may be useful against atherosclerosis.
Central Research Laboratories, ZERIA Pharmaceutical Co., Ltd., Saitama, Japan.
S
S
Ito
R
R
Higashino
T
T
Tanaka
M
M
Takei
T
T
Kurimoto
K
K
Matsuda
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D003864:Depression, Chemical; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D015737:Nisoldipine / Q000494:pharmacology; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008077:Lipoproteins, LDL; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine; D015737:Nisoldipine