Perturbation by lysophosphatidylcholine of membrane permeability in cultured vascular smooth muscle and endothelial cells.
Lysophosphatidylcholine (LPC), a major component of oxidized low-density lipoprotein found in atherosclerotic arterial walls, has been shown to have insignificant effect on arterial contraction but cause an impairment of endothelium-dependent relaxation (EDR). The aim of this study was to compare the degree of LPC-induced perturbation in the plasma membrane of cultured aortic smooth muscle cells (SMC) and endothelial cells (EC). In contractility studies phenylephrine (PE) elicited a sustained contraction and a subsequent addition of acetylcholine (ACh) caused an almost complete relaxation. Preincubation of endothelium-intact aortic rings with LPC did not significantly affect PE-elicited contraction but substantially inhibited ACh-triggered relaxation. Such inhibition by LPC was both concentration- and time-dependent. LPC also inhibited relaxation triggered by extracellular ATP and cyclopiazonic acid. Exposure of cultured EC to LPC (30 microM) resulted in an elevation of [Ca2+]i with a lag period of some 25 min. Following [Ca2+]i elevation, addition of Ni2+ resulted in a rapid entry of this ion into the cell. In addition, fura-2 leak-out was observed. Exposure of cultured SMC to 30 microM LPC also resulted in [Ca2+]i elevation and Ni2+ entry. However, LPC did not cause fura-2 leak-out in SMC. Also, LPC raised [Ca2+]i at a slower rate in SMC than in EC. Our results suggest that the plasma membrane of EC is more susceptible to LPC-induced derangement than that of SMC. This may contribute in part to the selective impairment of EDR by LPC.
Leung
Y M
YM
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Xion
Y
Y
Ou
Y J
YJ
Kwan
C Y
CY
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D005470:Fluorometry; D016257:Fura-2; D008244:Lysophosphatidylcholines / Q000493:pharmacokinetics*; D008297:Male; D008832:Microchemistry; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008244:Lysophosphatidylcholines; D016257:Fura-2