Cerebrovascular endothelial dysfunction mediated by beta-amyloid.
beta-Amyloid (A beta) toxicity has a critical role in the pathology of Alzheimer's disease (AD) but its function in the neurodegenerative process is not clearly established. Recently, we demonstrated a novel action of beta-amyloid on peripheral blood vessels: endothelial dysfunction through reactive oxygen species. Here we report the direct effect of A beta on cerebrovascular endothelium. Following treatment with A beta 1-40, bovine cerebral arteries showed characteristic features of endothelial dysfunction such as increased contraction to vasoconstrictor and diminished relaxation to endothelium-dependent vasodilators. Electron microscopy revealed significant damage to the endothelium by A beta. Pretreatment with the antioxidant superoxide dismutase (SOD) and PBN (n-tert-butyl-alpha-phenylnitrone) antagonized the effects of A beta. Endothelial damage induced by A beta could produce ischemic and inflammatory changes contributing to the pathology of AD.
Thomas
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Woodlands Medical Center, Oldsmar, FL 34677, USA.
McLendon
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Sutton
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Thomas
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D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D002536:Cerebral Arteries / Q000502:physiology*; D003497:Cyclic N-Oxides; D004730:Endothelium, Vascular / Q000502:physiology*; D016015:Logistic Models; D009589:Nitrogen Oxides / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C078592:amyloid beta-protein (1-40); C029217:phenyl-N-tert-butylnitrone; D013482:Superoxide Dismutase; D001920:Bradykinin