Aging enhances vascular dysfunction induced by the Alzheimer's peptide beta-amyloid.
Aging is a major risk factor for Alzheimer's disease and the evidence suggests a role for cerebrovascular pathology in cognitive dysfunction. The hypothesis in this study is that aging is a significant risk factor in the effect of the Alzheimer peptide beta-amyloid on endothelium-dependent function of cerebral and peripheral vessels. The diameter response to acetylcholine, an endothelium-dependent vasodilator, was recorded in pressurized segments of rat posterior cerebral vessels from mature (3 months) and aged (20 months) rats. The threshold concentration of beta-amyloid for a significant decrease in the response to acetylcholine was lower in vessels from aged rats (10(-9) M) than in vessels from mature rats (10(-8) M). The threshold concentration of beta-amyloid for a significant decrease in the sensitivity to acetylcholine was lower for ring segments of aorta from aged rats (10(-10) M) than for aorta from mature rats (10(-8) M). Structural changes of the endothelium were first observed in electron micrographs of aorta from aged rats when the concentration of beta-amyloid was 10(-8) M, whereas structural changes in aorta from mature rats did not occur until the concentration of beta-amyloid was increased to 10(-7) M. The results suggest that aging increases the susceptibility of cerebral and peripheral blood vessels to beta-amyloid related dysfunction and that functional change precedes structural change.
Price
Joel M
JM
Department of Physiology and Biophysics, University of South Florida, College of Medicine, Tampa, Florida 33612, USA. jprice@hsc.usf.edu
Hellermann
Alison
A
Hellermann
Gary
G
Sutton
E Truitt
ET
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D002536:Cerebral Arteries; D002561:Cerebrovascular Disorders / Q000139:chemically induced*; D004056:Differential Threshold / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D000109:Acetylcholine