Prevention of fatty streak formation of 17beta-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.


RESULTS
In the present work, the respective roles of 17beta-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 x kg(-1) x 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
17Beta-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 17beta-estradiol, leading to a complete dissociation between circulating MDA-modified LDL and parietal lesions.
Elhage
R
R
INSERM U397 and Laboratoire de Physiologie, Institut L. Bugnard, Toulouse, France.
Bayard
F
F
Richard
V
V
Holvoet
P
P
Duverger
N
N
Fiévet
C
C
Arnal
J F
JF
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000517:prevention & control*; D004958:Estradiol / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*
D001057:Apolipoproteins E; D009569:Nitric Oxide; D004958:Estradiol; D019331:NG-Nitroarginine Methyl Ester