Lysophosphatidylcholine Attenuates Endothelium-dependent Relaxation Responses through Inhibition of ACh-induced Endothelial [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> Increase

Lysophosphatidylcholine Attenuates Endothelium-dependent Relaxation Responses through Inhibition of ACh-induced Endothelial [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> Increase

Lysophosphatidylcholine (LPC), which accumulates in atherosclerotic arteries, has been reported to inhibit endothelium-dependent relaxation (EDR) in many different species. However, the underlying mechanism of LPC-induced inhibition of EDR is still uncertain. In the present study, we measured simultaneously both isometric tension and cytosolic free Ca<SUP>2&#8290;</SUP> ([Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>) in rabbit carotid strips, and examined the effect of LPC on tension and [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>. In carotid strips with intact-endothelium, high K<SUP>&#8290;</SUP> (70 mM) increased both tension and [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>, and cumulative addition of acetylcholine (ACh) from 0.1 to 10μM induced dose dependent increase of [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> with concomitant relaxation. In the presence of L-NAME (0.1 mM), ACh increased [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> without affecting the amplitude of high K<SUP>&#8290;</SUP>-induced tension. These ACh-induced change of [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> and tension was abolished by removal of endothelium or 10 nM 4-DAMP (muscarinic receptor antagonist) pretreatment. Pretreatment of LPC (10μM) inhibited ACh (10μM)-induced change of tension and [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> in endothelium-intact carotid artery. On the other hand, LPC had no effect on ACh-induced change of tension and [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> in endothelium denuded artery. In Ca<SUP>2&#8290;</SUP>-free external solution, ACh transiently increased [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>, and pretreatment of LPC significantly inhibited ACh-induced transient [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> change. Based on the above results, it may be concluded that LPC inhibits the ACh-induced [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> change through inhibition of Ca<SUP>2&#8290;</SUP> mobilization in vascular endothelial cells, resulting in decreased production of NO and concomitant inhibition of endothelium- dependent vascular relaxation.