title: Effect of native and oxidized low-density lipoprotein on endothelial nitric oxide and superoxide production : key role of L-arginine availability.
abstract: BACKGROUND
  Native and oxidized LDLs (n-LDL and ox-LDL) are involved in the atherogenic process and affect endothelium-dependent vascular tone through their interaction with nitric oxide (NO).
  
  
  RESULTS
  In this study we evaluated directly, by using a porphyrinic microsensor, the effect of increasing lipoprotein concentrations on endothelial NO and superoxide (O(2)(-)) production. We investigated where lipoproteins may affect the L-arginine-NO pathway by pretreating cells with L-arginine, L-N-arginine methyl ester (L-NAME), and superoxide dismutase. Bovine aortic endothelial cells were exposed for 1 hour to increasing concentrations of n-LDL (from 0 to 240 mg cholesterol/dL) and ox-LDL (from 0 to 140 mg cholesterol/dL). A stimulated (calcium ionophore) NO concentration decreased to 29% of the control at n-LDL concentration of 80 mg cholesterol/dL and to 15% of the control at 20 mg cholesterol/dL of ox-LDL. L-Arginine partially neutralized the inhibitory effect of n-LDL and ox-LDL on the NO generation. Superoxide dismutase pretreatment did not modify NO production, whereas L-NAME blunted NO generation at all LDL concentrations. O(2)(-) production was increased at low n-LDL and very low ox-LDL concentrations; this was reversed by L-arginine.
  
  
  CONCLUSIONS
  These findings confirm the inhibitory role of n-LDL and ox-LDL on NO generation and suggest that lipoproteins may induce a decreased uptake of L-arginine. The local depletion of the L-arginine substrate may derange the NO synthase, leading to overproduction of O(2)(-) from oxygen, the other substrate of NO synthase.
authors.affiliation: Second Department of Internal Medicine, University of Ferrara, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Vergnani
authors.forename: S
authors.initials: S
authors.lastname: Hatrik
authors.forename: F
authors.initials: F
authors.lastname: Ricci
authors.forename: A
authors.initials: A
authors.lastname: Passaro
authors.forename: N
authors.initials: N
authors.lastname: Manzoli
authors.forename: G
authors.initials: G
authors.lastname: Zuliani
authors.forename: V
authors.initials: V
authors.lastname: Brovkovych
authors.forename: R
authors.initials: R
authors.lastname: Fellin
authors.forename: T
authors.initials: T
authors.lastname: Malinski
mesh_terms: D000818:Animals; D001120:Arginine / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine