BETA-AMYLOID INDUCES CEREBROVASCULAR ENDOTHELIAL DYSFUNCTION IN THE RAT-BRAIN

beta-Amyloid toxicity plays a central role in the pathology of Alzheim er's disease. Contraction and relaxation responses of pressurized rat posterior cerebral artery were studied before and after in vitro expos ure to beta-amyloid. The peptide-induced characteristic features of en dothelial dysfunction including enhanced vasoconstriction with seroton in and diminished relaxation to endothelium-dependent vasodilators ace tylcholine and bradykinin. Response to the endothelium-independent vas odilator nitroprusside was not affected by beta-amyloid. beta-amyloid inhibition of acetylcholine-induced vasodilation was prevented by the oxygen radical scavenging enzyme superoxide dismutase. Endothelial des truction and the protective effect of superoxide dismutase was verifie d by electron microscopy. The results suggest that beta-amyloid peptid e produces endothelial dysfunction in cerebral microvessels through re active oxygen species.