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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Antiatherogenic effects of S-nitroso-N-acetylcysteine in hypercholesterolemic LDL receptor knockout mice

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Krieger, M. H. ; Santos, K. F. R. ; Shishido, S. M. ; Wanschel, A. C. B. A. ; Estrela, H. F. G. ; Santos, L. ; Oliveira, M. G. de ; Franchini, K. G. ; Spadari-Bratfisch, R. C. ; Laurindo, F. R. M. [10]
Total Authors: 10
Document type: Journal article
Source: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 14, n. 1, p. 12-20, Feb. 2006.
Field of knowledge: Biological Sciences - Physiology

The pathophysiology of the NO/NO synthase system and dysfunctional changes in the endothelium in the early phases,of the atherogenic process are incompletely understood. In this study, we investigated the effects of the nitrosothiol NO donor S-nitroso-N-acetylcysteine (SNAC) in the early prevention of plaque development in the hypercholesterolemic LDLr-/- mice as well as the changes in endothelium-dependent relaxation and NO synthase expression. LDLr-/- mice were fed a 1.25% cholesterol-enriched diet for 15 days. Plasma cholesterol/triglyceride levels increased and this increase was accompanied by the development of aortic root lesions. Aortic vasorelaxation to acetylcholine was increased, although endothelium-independent relaxation in response to sodium nitroprusside did not change, which suggest stimulated NO release enhanced. This dysfunction was associated with enhanced aortic superoxide production and with increased levels of constitutive NOS isoform expression, particularly neuronal NOS. SNAC (S-nitroso-N-acetyleysteine) administration (0.51 mu mol/kg/day i.p. for 15 days) decreased the extent of the plaque by 55% in hypercholesterolemic mice, but had no effects on vasomotor changes. It did, however, lead to a decrease in constitutive NOS expression. The SNAC induced only minor changes in plasma lipid profile. The present study has shown that, in early stages of plaque development in LDLr-/- mice, specific changes in NO/NO synthase system develop, that are characterized by increased endothelium-dependent vasorelaxation and increased constitutive NOS expression. Since the development of plaque and the indicator of endothelial cell dysfunction were prevented by SNAC, such treatment may constitute a novel strategy for the halting of progression of early plaque. (AU)

FAPESP's process: 00/12154-2 - Molecular physiology of redox signaling in the vascular system and cultured cell models
Grantee:Francisco Rafael Martins Laurindo
Support type: Research Projects - Thematic Grants