Phenyl-N-tert-butyl nitrone neutralizes the activities of beta-amyloid peptides in both cultured cells and isolated vessels

Several lines of evidence suggest that the beta-amyloid (A beta) peptides a re partially responsible for the pathogenesis of Alzheimer's disease (AD). Our recent studies indicate that A beta-induced cerebral vascular dysfuncti on may play a significant role in the development of the disease. For examp le, A beta induces vascular endothelial cell death and enhances vasoconstri ction. Since excess free radicals and increased cytosolic calcium have been suggested to be involved in A beta-induced cellular and vascular dysfuncti on, we screened several kinds of antioxidants and calcium channel modulator s in both cultured cells and isolated vessels for their ability to prevent these effects. We found that, while some agents could partially prevent eit her A beta cytotoxicity or vasoactivity, a spin trapping agent, phenyl N-te rtbutyl nitrone (PBN), completely blocks A beta-enhanced vasoconstriction a nd protects both vascular endothelial and neuronal cells from A beta-induce d death.