In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 11 ( 2000-03-21), p. 1261-1266
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). Methods and 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.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.101.11.1261
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2000
detail.hit.zdb_id:
1466401-X
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