الفهرس 
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Abstract
The endothelium provides a cellular lining to all blood vessels in the circulatory system. The endothelium is now recognized as the most important component of normal vascular homeostasis, because it serves to maintain the anticoagulant, antiplatelet, and fibrinolytic phenotypes of vascular cells through the release of numerous dilator and constrictor substances. The most important factor released by the endothelium is nitric oxide (NO).
The partial loss of balance between endothelium-mediated vasodilation and vasoconstriction is described as vascular endothelial dysfunction (VED).
Nicotine exposure is considered to be a major risk factor involved in the induction and progression of cardiovascular disorders. In this study, Nicotine was injected to produce VED in rabbits.
Chronic administration of nicotine produced VED indicated by decreased serum NOx, generation of high degree of oxidative stress indicated by increased serum MDA level and deceased serum GSH and SOD activities, alteration in lipid profile indicated by increased serum total cholesterol (TC), triglycerides (TGs) and low density lipoprotein-cholesterol (LDL-C) levels and decreased serum high density lipoprotein-cholesterol (HDL-C) level, and increased VCAM-1 level and NF-κB protein expression.
Treatment with L-NAME led to impairment in the vascular endothelium functions indicated from decreased serum NOx, generation of high degree of oxidative stress, alteration in lipid profile indicated by increased serum TC, TGs and LDL-C levels and decreased serum HDL-C level, and increased VCAM-1 level and NF-κB protein expression.
Treatment with agmatine and lipoic acid markedly prevented the development of experimental VED induced by nicotine in rabbits. The vascular protecting potential of AG in preventing the development of VED may be attributed to its ability to improve the lipid profile beside its ability to improve NO production and reduce the oxidative stress and subsequent inhibition of VCAM-1 expression. Such effect of AG is mainly due to activation of eNOS activity beside alteration of the intracellular signaling including the NF-κB pathway. The beneficial effect of LA reflected by improving the lipid profile and increasing NO production was achieved not only by scavenging free radicals, but also by inhibition of NF-κB activation and VCAM-1 expression.