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Effects of native and oxidized low-density lipoproteins on endothelium-dependent and endothelium-independent vasomotion

  • J.-Chr. Galle
  • E. Bassenge
Conference paper

Summary

Native and oxidized low-density lipoproteins (LDL) were investigated for their direct influence on EDRF-formation, EDRF-activity, and vascular smooth muscle tone. Native (n) LDL, isolated from fresh human plasma, was oxidized by Cu2+-incubation. EDRF released from cultured endothelial cells was inactivated by both n-LDL and ox-LDL (1 mg/ml) as detected in a bioassay system. n-LDL reduced the EDRF-mediated vasodilations of the detector segments by 38.5±5.3%, and ox-LDL by 55.5±4.6%. The effects of lipoproteins on EDRF-formation were studied on cultured endothelial cells, preincubated with either n-LDL or ox-LDL (1 mg/ml, 1 h) and stimulated for EDRF-release with bradykinin after washout of the lipoproteins. EDRF was assessed by measuring its stimulatory effect on the activity of a purified soluble guanylate cyclase. Preincubation with both n-LDL and ox-LDL did not reduce the bradykinin-induced EDRF-formation. Accordingly, acetylcholine-induced, EDRF-mediated dilations of intact rabbit femoral artery segments were not impaired by luminal exposure to n-LDL or ox-LDL (1 h, 1 mg/ml).

Effects of n-LDL and ox-LDL on vascular smooth muscle tone were investigated in isolated perfused rabbit femoral arteries. Perfusion of endothelium-intact and -denuded segments with ox-LDL (80–500 μg protein/ml) caused no or only weak vascoconstrictions in the absence of contractile agonists. However, in the presence of ox-LDL, vasoconstrictions to threshold concentrations of norepinephrine (NE), serotonin (5-HT), phenylephrine (PE) or potassium were significantly enhanced. Native LDL (80–1000 μg/ml) had no effect on vascular tone, neither in presence nor in absence of contractile agonists. Preincubation with verapamil, diltiazem, and nitrendipine inhibited vasoconstrictions evoked by ox-LDL. The contractile responses to ox-LDL were significantly greater in endothelium-denuded segments than in endothelium-intact segments.

In conclusion, neither n-LDL nor ox-LDL acutely impair the formation of EDRF, but do inactivate EDRF after its release from endothelial cells. n-LDL has no direct influence on vascular smooth muscle tone, but ox-LDL greatly enhances vasoconstrictions to various contractile agonists by direct interaction with vascular smooth muscle. Thus, in regions of lipoprotein-accumulation in the arterial wall, both n-LDL and ox-LDL may favor inappropriate vasoconstrictions.

Key words

Hypercholesterolemia atherosclerosis vasospasm endothelium-derived relaxant factor (EDRF) vascular smooth muscle lipid peroxidation 

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Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt 1991

Authors and Affiliations

  • J.-Chr. Galle
    • 1
    • 2
  • E. Bassenge
    • 2
  1. 1.Institut für Angewandte Physiologie und BalneologieUniversität FreiburgFreiburgGermany
  2. 2.Department of Applied PhysiologyUniversity of FreiburgGermany

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