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Inhibition of endothelium-dependent vascular relaxation by lysophosphatidylcholine: Impact of lysophosphatidylcholine on mechanisms involving endothelium-derived nitric oxide and endothelium derived hyperpolarizing factor

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Abstract

Hyperlipidemia has been associated with an increase in the incidence of atherosclerosis. The oxidation of low density lipoprotein (LDL) plays an important role in the initiation and progression of atherosclerosis, one of its effects being the inhibition of endothelium dependent relaxation (EDR). The elevated level of lysophosphatidylcholine (LPC) in oxidatively modified LDL has been shown to be a biochemical factor responsible for the impairment of EDR in vascular ring preparations. Several endothelium-derived modulators are thought to control vascular responsiveness. The present work examined whether acetylcholine (ACh)-induced EDR in rat aorta (pre-contracted with phenylephrine, PE) involved both endothelium-derived nitric oxide (EDNO) and endothelium-dependent hyperpolarizing factor (EDHF) and whether LPC inhibited either of these selectively. Indomethacin (10-5 M), had no significant effect on EDR, indicating that products of cyclooxygenase, including prostacyclin, are not involved. Treatment with either NW-nitro-L-arginine methyl ester (L-NAME, 6.8 μM) to inhibit the production of EDNO or with elevated K+ (15 mM), to block the hyperpolarizing effect of EDHF impaired EDR considerably (each of these shifting the inhibitory dose-response relationship to ACh by almost one log unit); in muscles treated with both of these agents EDR was completely inhibited. In each of L-NAME- and K-treated muscles, the addition of LPC (20 μM) further impaired EDR. LPC did not independently raise the tone of resting- or PE-contracted aorta. We conclude that the inhibition of EDR of rat aorta by LPC involves the actions of both EDNO and EDHF.

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Authors and Affiliations

  1. Lipid Research Group, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

    D.E. Froese, J. McMaster, P.C. Choy & E.A. Kroeger

  2. Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong

    R.Y.K. Man

Authors
  1. D.E. Froese
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  2. J. McMaster
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  3. R.Y.K. Man
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  4. P.C. Choy
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  5. E.A. Kroeger
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Froese, D., McMaster, J., Man, R. et al. Inhibition of endothelium-dependent vascular relaxation by lysophosphatidylcholine: Impact of lysophosphatidylcholine on mechanisms involving endothelium-derived nitric oxide and endothelium derived hyperpolarizing factor. Mol Cell Biochem 197, 1–6 (1999). https://doi.org/10.1023/A:1006847929334

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