ALPHA-TOCOPHEROL PRETREATMENT IMPROVES ENDOTHELIUM-DEPENDENT VASODILATION IN AORTIC STRIPS OF YOUNG AND AGING RATS EXPOSED TO OXIDATIVE STRESS

Acetylcholine-induced, endothelium-dependent relaxation of norepinephr ine-precontracted aortic strips, was severely impaired after exposure to a hypoxanthine/xanthine oxidase reaction generating oxygen radicals . This effect was more evident in aortic strips of aging rats (24 mont hs old) in comparison to young rats (3 months old). The addition of au thentic . NO (1 mu M) completely relaxed aortic strips exposed to oxid ative stress both in young and aging rats. In vitro EPR measurements s howed that the . NO signal was reduced by enzymatic O-2(radical anion) generating reaction. The activity of a partial purified preparation o f constitutive NO synthase from rat cerebellum was significantly decre ased after exposure to exogenous oxygen radicals. Pretreatment of aort ic strips with 100 mu M alpha-tocopherol-phosphate, produced a signifi cant improvement of acetylcholine-dependent relaxation in the aortic s trips exposed to oxidative stress, particularly in the aged vessel. Th e content of malondialdehyde in aortic tissue did not change after oxi dative stress or alpha-tocopherol pre-treatment. Alpha-tocopherol was unable to recover the NO synthase activity depressed in vitro by hypox anthine/xanthine oxidase reaction. This study confirms that an oxidati ve stress impairs the endothelium-mediated vasodilation. Alpha-tocophe rol pre-treatment protects the vessel against this damage. The mechani sm of action of alpha-tocopherol is unknown, but seems unrelated to an antioxidant activity.