ABSTRACT
BACKGROUND: 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. METHODS AND RESULTS: 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-acetylcysteine) administration (0.51 micromol/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. CONCLUSION: 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.
Subject(s)
Acetylcysteine/analogs & derivatives , Atherosclerosis/prevention & control , Hypercholesterolemia/drug therapy , Nitric Oxide Donors/therapeutic use , Receptors, LDL/physiology , Acetylcysteine/therapeutic use , Animals , Blotting, Western , Hypercholesterolemia/enzymology , Immunohistochemistry , Mice , Mice, Knockout , Nitric Oxide Synthase/metabolism , Receptors, LDL/geneticsABSTRACT
A aterosclerose pode ser considerada uma doença na circulaçäo coronariana. O presente trabalho estuda a açÄo da quercetina, morina, ácido nicotínico de maneira isolada e em associaçÄo envolvendo quercetina + ácido nicotínico e morina + ácido nicotínico no metabolismo lipídico. Foram dosados colesterol, colesterol-HDL e triacilglicerol após administraçäo de duas doses dos compostos morina, quercetina, morina + ácido nicotínico e quercetina + ácido nicotínico sendo a primeira imediatamente após a administraçäo do triton e a segunda dose, vinte horas depois. Decorridos quarenta e três horas após a administraçäo do triton o sangue foi analisado. Os resultados mostraram que morina + ácido nicotínico e quercetina + ácido nicotínico apresentaram os melhores resultados para colesterol (-83,77 porcento e 74,42 porcento). Para colesterol-HDL os melhores resultados foram com morina e com associaçäo quercetina + ácido nicotínico (+17,99 porcento e +21,96 porcento). Morina + ácido nicotínico mostraram os melhores níveis para triacilgliceróis (-83,77 porcento)
