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

Takayama M, Yao K, Wada M - J. Biomed. Sci. (2009)

Bottom Line: We examined the effects of benidipine on the impairment of endothelium-dependent relaxation induced by LPC.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.The present findings may provide new insights into the endothelial protective effects of benidipine.

View Article: PubMed Central - HTML - PubMed

Affiliation: Pharmaceutical Research Center, Kyowa Hakko Kirin Co, Ltd, Sunto-gun, Shizuoka-ken, Japan. makoto.takayama@kyowa-kirin.co.jp

ABSTRACT

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 LPC-induced 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.

Conclusion: 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.

Show MeSH

Related in: MedlinePlus

Tracings showing relaxant response to ACh (endothelium-dependent vasodilator) in isolated rat aorta. Benidipine or vehicle was administered orally to rats. Thoracic aortas were isolated at 90 min following benidipine administration. Aortas were cut into rings, and incubated with LPC (5 μmol/L) or ethanol (0.05%) for 60 min. After washing, the rings were pre-contracted using PE (1 μmol/L) and subsequently relaxed using ACh. ACh evoked relaxation in the aortic ring isolated from vehicle-treated rat (A). EDR was markedly attenuated following incubation with LPC (B). LPC-induced attenuation of EDR was inhibited in benidipine-treated rat (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2710319&req=5

Figure 1: Tracings showing relaxant response to ACh (endothelium-dependent vasodilator) in isolated rat aorta. Benidipine or vehicle was administered orally to rats. Thoracic aortas were isolated at 90 min following benidipine administration. Aortas were cut into rings, and incubated with LPC (5 μmol/L) or ethanol (0.05%) for 60 min. After washing, the rings were pre-contracted using PE (1 μmol/L) and subsequently relaxed using ACh. ACh evoked relaxation in the aortic ring isolated from vehicle-treated rat (A). EDR was markedly attenuated following incubation with LPC (B). LPC-induced attenuation of EDR was inhibited in benidipine-treated rat (C).

Mentions: PE induced contraction and ACh elicited relaxation in isolated muscle strips from rat thoracic aortas (Figure 1A). ACh-induced relaxation was markedly impaired following LPC challenge (Figure 1B, 2A, B and 2C). Orally administered benidipine inhibited LPC-induced attenuation of EDR (Figure 1C and 2A). In contrast, amlodipine and nifedipine did not affect LPC-induced attenuation of EDR (Figure 2B and 2C). Benidipine, amlodipine and nifedipine did not significantly inhibit PE-induced contraction (data not shown).


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

Takayama M, Yao K, Wada M - J. Biomed. Sci. (2009)

Tracings showing relaxant response to ACh (endothelium-dependent vasodilator) in isolated rat aorta. Benidipine or vehicle was administered orally to rats. Thoracic aortas were isolated at 90 min following benidipine administration. Aortas were cut into rings, and incubated with LPC (5 μmol/L) or ethanol (0.05%) for 60 min. After washing, the rings were pre-contracted using PE (1 μmol/L) and subsequently relaxed using ACh. ACh evoked relaxation in the aortic ring isolated from vehicle-treated rat (A). EDR was markedly attenuated following incubation with LPC (B). LPC-induced attenuation of EDR was inhibited in benidipine-treated rat (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2710319&req=5

Figure 1: Tracings showing relaxant response to ACh (endothelium-dependent vasodilator) in isolated rat aorta. Benidipine or vehicle was administered orally to rats. Thoracic aortas were isolated at 90 min following benidipine administration. Aortas were cut into rings, and incubated with LPC (5 μmol/L) or ethanol (0.05%) for 60 min. After washing, the rings were pre-contracted using PE (1 μmol/L) and subsequently relaxed using ACh. ACh evoked relaxation in the aortic ring isolated from vehicle-treated rat (A). EDR was markedly attenuated following incubation with LPC (B). LPC-induced attenuation of EDR was inhibited in benidipine-treated rat (C).
Mentions: PE induced contraction and ACh elicited relaxation in isolated muscle strips from rat thoracic aortas (Figure 1A). ACh-induced relaxation was markedly impaired following LPC challenge (Figure 1B, 2A, B and 2C). Orally administered benidipine inhibited LPC-induced attenuation of EDR (Figure 1C and 2A). In contrast, amlodipine and nifedipine did not affect LPC-induced attenuation of EDR (Figure 2B and 2C). Benidipine, amlodipine and nifedipine did not significantly inhibit PE-induced contraction (data not shown).

Bottom Line: We examined the effects of benidipine on the impairment of endothelium-dependent relaxation induced by LPC.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.The present findings may provide new insights into the endothelial protective effects of benidipine.

View Article: PubMed Central - HTML - PubMed

Affiliation: Pharmaceutical Research Center, Kyowa Hakko Kirin Co, Ltd, Sunto-gun, Shizuoka-ken, Japan. makoto.takayama@kyowa-kirin.co.jp

ABSTRACT

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 LPC-induced 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus