beta-Amyloid induces cerebrovascular endothelial dysfunction in the rat brain.
beta-Amyloid toxicity plays a central role in the pathology of Alzheimer's disease. Contraction and relaxation responses of pressurized rat posterior cerebral artery were studied before and after in vitro exposure to beta-amyloid. The peptide-induced characteristic features of endothelial dysfunction including enhanced vasoconstriction with serotonin and diminished relaxation to endothelium-dependent vasodilators acetylcholine and bradykinin. Response to the endothelium-independent vasodilator 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 destruction and the protective effect of superoxide dismutase was verified by electron microscopy. The results suggest that beta-amyloid peptide produces endothelial dysfunction in cerebral microvessels through reactive oxygen species.
Price
J M
JM
Department of Physiology and Biophysics, University of South Florida, Tampa, USA.
Sutton
E T
ET
Hellermann
A
A
Thomas
T
T
D000109:Acetylcholine / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000503:physiopathology* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology* / Q000648:ultrastructure; D016166:Free Radical Scavengers / Q000494:pharmacology; D008854:Microscopy, Electron; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D013482:Superoxide Dismutase; D000109:Acetylcholine; D001920:Bradykinin