Effects of native and oxidized low density lipoproteins on formation and inactivation of endothelium-derived relaxing factor.
The influence of native (N-) and oxidized (Ox-) low density lipoproteins (LDLs) on endothelium-dependent vasomotion is still controversial. We investigated the short-term effects of N-LDL and Ox-LDL on the formation of endothelium-derived relaxing factor (EDRF) in native and cultured endothelial cells and on its inactivation after release from the cells. N-LDL was isolated from fresh human plasma via sequential ultracentrifugation and oxidized by incubation with Cu2+. 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 in cultured endothelial cells preincubated with either N-LDL or Ox-LDL (1 mg/ml for 1 hour) 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. Both N-LDL and Ox-LDL did not reduce the bradykinin-induced EDRF formation. Consistent with this finding, acetylcholine-induced, EDRF-mediated dilations of intact rabbit femoral artery segments were not impaired by luminal exposure to N-LDL or Ox-LDL (1 mg/ml for 1 hour). However, these relaxations were significantly reduced by preincubation of aortic ring preparations with the same concentrations of the same charges of N-LDL and Ox-LDL. In conclusion, neither N-LDL nor Ox-LDL acutely impairs the formation of EDRF but does inactivate EDRF after its release from endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Galle
J
J
Institute of Applied Physiology, University of Freiburg, F.R.G.
Mülsch
A
A
Busse
R
R
Bassenge
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects
D008077:Lipoproteins, LDL; D009569:Nitric Oxide; D000109:Acetylcholine