The dihydropyridine calcium channel blocker benidipine prevents lysophosphatidylcholine-induced endothelial dysfunction in rat aorta

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.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.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.One of the pathological manifestations in atherosclerosis is the dysfunction of vascular endothelial cells [1]. Oxidized low-density lipoprotein (ox-LDL) is known to accumulate in atherosclerotic arterial walls [2]. A major bioactive ingredient of ox-LDL appears to be lysophosphatidylcholine (LPC), as this lysolipid can inhibit endothelium-dependent relaxation (EDR) [3,4]. One mechanism by which LPC causes impairment of EDR is to inhibit the release of nitric oxide (NO), which is dependent upon the intracellular calcium concentration ([Ca2+]i) [3,4]. The mechanism by which LPC interacts with endothelial cells to facil