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 incr ease endothelial NO synthase expression in castrated animals and to pr event the degradation of NO by decreasing superoxide anion production in cultured endothelial cells. In both cases, increased NO bioavailabi lity would promote vasodilation, inhibit proliferation of the adjacent vascular smooth muscle, reduce platelet aggregation, and inhibit mono cyte adhesion to the endothelium and the inflammatory reaction induced by cytokines. all key contributors in the development of atherosclero sis. Methods and Results In the present work, the respective roles of 17 beta-estradiol and NO in the development of the atherosclerotic pro cess were investigated in castrated apolipoprotein E-deficient (apo E KO) mice, which spontaneously develop fatty streak lesions within 3 mo nths. N-omega-Nitro-L-arginine methyl ester (L-NAME), an NO synthase i nhibitor, 50 mg . kg(-1) . d(-1), increased arterial blood pressure an d 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 th e aortic lesions approximately threefold, and the magnitude of this va sculoprotective effect was not altered by L-NAME. Moreover, L-NAME inc reased circulating malonyldialdehyde (MDA)-modified LDL, which was not altered by 17 beta-estradiol, leading to a complete dissociation betw een circulating MDA-modified LDL and parietal lesions.