Prevention of fatty streak formation of 17 beta-estradiol is not mediated by the production of nitric oxide in apolipoprotein E-deficient mice

Background Estrogens have atheroprotective properties, the mechanisms of which remain obscure. Estrogens have recently been reported to increase endothelial NO synthase expression in castrated animals and to prevent the degradation of NO by decreasing superoxide anion production in cultured endothelial cells. In both cases, increased NO bioavailability would promote vasodilation, inhibit proliferation of the adjacent vascular smooth muscle, reduce platelet aggregation, and inhibit monocyte adhesion to the endothelium and the inflammatory reaction induced by cytokines. all key contributors in the development of atherosclerosis. Methods and Results In the present work, the respective roles of 17 beta-estradiol and NO in the development of the atherosclerotic process were investigated in castrated apolipoprotein E-deficient (apo E KO) mice, which spontaneously develop fatty streak lesions within 3 months. N-omega-Nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, 50 mg . kg(-1) . d(-1), increased arterial blood pressure and decreased cerebellum cGMP content, demonstrating the blockade of NO production, but did not influence the atherogenic process in castrated apo E KO mice. Conclusions 17 beta-Estradiol decreased the size of the aortic lesions approximately threefold, and the magnitude of this vasculoprotective effect was not altered by L-NAME. Moreover, L-NAME increased circulating malonyldialdehyde (MDA)-modified LDL, which was not altered by 17 beta-estradiol, leading to a complete dissociation between circulating MDA-modified LDL and parietal lesions.