Role of endogenous nitric oxide in progression of atherosclerosis in apolipoprotein E-deficient mice

This study investigated the role of endogenous nitric oxide (NO) in the pro gression of atherosclerosis in apolipoprotein E-deficient [apoE-knockout (K O)] mice. Mice were treated with N-omega-nitro-L-arginine methyl ester (L-N AME) an inhibitor of nitric oxide synthase (NOS) or with the NOS substrate L-arginine for 8 wk. L-NAME treatment resulted in a significant inhibition of NO-mediated vascular responses and a significant increase in the atheros clerotic plaque/surface area in the aorta of apoE-KO mice. L-arginine treat ment had no influence on endothelial function and did not alter lesion size . Mean arterial blood pressure and serum Lipid levels were not altered by t he treatments. At the beginning of the study impairment in endothelial func tion was only apparent in the case of N-G-nitro-L-arginine-induced, NO-medi ated contraction, whereas ACh-induced, NO-mediated relaxation was not diffe rent between age-matched apoE-KO and C57B1/6J mice. After the 8-wk treatmen t with the NOS inhibitor, both NO-mediated responses were significantly inh ibited. The acceleration in lesion size concomitant to the severely impaire d NO-mediated responses indicates that lack of endogenous NO is an importan t progression factor of atherosclerosis in the apoE-KO mouse.