These data suggest that eccentric ISMN can completely inhibit the increase of vascular bioavailability of superoxide and partially prevent intimal lesion formation and endothelial dysfunction in hypercholesterolemia.
We sought to determine the e¡ects of the superoxide dismutase (SOD) inhibitor diethyldithiocarbamate (DETC) on vascular superoxide production. Rat aortic rings treated with DETC (10 mM) showed no change of superoxide generation (5 W WM lucigenin). Likewise, DETC did not change the expression and activity of vascular soluble guanylyl cyclase, an enzyme known to be extremely sensitive to superoxide. In striking contrast, DETC completely inhibited the superoxide production induced by 6-anilino-5,8-quinolinedione (LY83583) and abolished the catalytic activity of xanthine oxidase (XO). Thus, DETC inhibits vascular superoxide production by blocking oxidoreductase enzymes such as XO and those reducing LY83583 in rat aorta. ß
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