Beta-amyloid-induced coronary artery vasoactivity and endothelial damage.
Amyloid beta-peptide (A beta) deposition has been associated with coronary heart disease and neurodegenerative diseases. A link between A beta and free radical generation has been explored in neuronal tissue. We report here on the effect of A beta on pressurized segments of coronary resistance arteries and the role of free radicals. A small oscillatory response to A beta (10[-6] M) that consisted of a relaxation followed by constriction and a return to the basal diameter was observed in all vessels. The thromboxane A2 analog U46619 produced a significantly greater constriction compared with the response before treatment with A beta. The presence of the antioxidant enzyme superoxide dismutase (SOD) reduced both the response to A beta alone and the enhanced response to U46619. Vasodilation responses to acetylcholine (10[-9]-10[-5] M) were virtually eliminated at all concentrations by A beta. We confirmed endothelial cell damage by A beta with electron microscopy. The results suggest that A beta deposition in coronary resistance arteries causes endothelial damage that is mediated through superoxide radicals.
Thomas
T
T
Department of Psychiatry, University of South Florida, College of Medicine, Tampa 33612-4799, U.S.A.
Sutton
E T
ET
Hellermann
A
A
Price
J M
JM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000375:Aging / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000648:ultrastructure; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013482:Superoxide Dismutase