A beta vasoactivity in vivo.
Bilateral temporoparietal hypoperfusion has been frequently observed early in the Alzheimer's disease (AD) process. The beta-amyloid (A beta) peptide is believed to play a central role in the pathogenesis of AD. In vitro experiments have shown that freshly solubilized A beta enhances constriction of cerebral and peripheral vessels. We proposed that in vivo, A beta would also have vasoactive properties. To test this hypothesis, we intraarterially infused freshly solubilized A beta 1-40 in rats and observed changes in peripheral blood pressure, cerebral blood flow, and cerebrovascular resistance. We found that infusion of A beta in vivo significantly increased the blood pressure in hypotensive rats but not in normotensive and hypertensive rats. Moreover, A beta infusion also resulted in a decreased blood flow and increased vascular resistance specifically in cerebral cortex but not in heart or kidneys. These data suggest that A beta has a direct and specific constrictive effect on cerebral vessels in vivo, which may contribute to the cerebral hypoperfusion observed early in the AD process.
Suo
Z
Z
Roskamp Institute, Tampa, Florida 33613, USA. zsuo@com1.med.usf.edu
Su
G
G
Placzek
A
A
Kundtz
A
A
Humphrey
J
J
Crawford
F
F
Mullan
M
M
D000682:Amyloid / Q000008:administration & dosage / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002540:Cerebral Cortex / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D058228:Islet Amyloid Polypeptide; D007668:Kidney / Q000098:blood supply; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)