- 作者: Makoto Takayama; Kozo Yao; Michihito Wada
- 作者服務機構: Pharmacological Research Laboratories, Pharmaceutical Research Center, Kyowa Hakko Kirin Co., Ltd., Japan.
- 中文摘要: --
- 英文摘要:
Background :
Lysophosphatidylcholine (LPC), an atherogenic component of oxidized low-density
lipoprotein, has been shown to induce the attenuation of endothelium-dependent
vascular relaxation. Although benidipine, a dihydropyridine-calcium channel blocker,
is known to have endothelial protective effects, the effects of benidipine on LPCinduced
endothelial dysfunction remain unknown. We examined the effects of
benidipine on the impairment of endothelium-dependent relaxation induced by LPC.
Methods :
Benidipine was administered orally to rats and aortas were then isolated. Aortic rings
were treated with LPC and endothelial functions were then evaluated. Additionally,
the effects of benidipine on intracellular calcium concentration ([Ca2+]i) and
membrane fluidity altered by LPC in primary cultured rat aortic endothelial cells were
examined. [Ca2+]i was measured using the fluorescent calcium indicator fura-2.
Membrane fluidity was monitored by measuring fluorescence recovery after
photobleaching.
Results :
Treatment with LPC impaired endothelial function. Benidipine prevents the
impairment of relaxation induced by LPC. Acetylcholine elicited an increase in
[Ca2+]i in fura-2 loaded endothelial cells. The increase in [Ca2+]i was suppressed after
exposure to LPC. Plasma membrane fluidity increased following incubation with
LPC. Benidipine inhibited the LPC-induced increase in membrane fluidity and
impairment of increase in [Ca2+]i.
Conclusions :
These results suggest that benidipine inhibited LPC-induced endothelial dysfunction
by maintaining increase in [Ca2+]i. Benidipine possesses membrane stabilization
properties in LPC-treated endothelial cells. It is speculated that the preservation of
membrane fluidity by benidipine may play a role in the retainment of calcium
mobilization. The present findings may provide new insights into the endothelial
protective effects of benidipine. - 中文關鍵字: --
- 英文關鍵字: --