The vasoactivity of A beta peptides.
We have demonstrated that freshly solubilized A beta peptides can enhance vasoconstriction by phenylephrine or endothelin of isolated rat aorta. Concentrations of peptide producing these effects (100 nM-1 microM) are much lower than those requiring toxicity to endothelial cells in culture, and effects are immediate, not requiring the prolonged time periods for aggregation necessary in A beta cell culture toxicity experiments. Pre-treatment with SOD diminishes the enhancement of vasoconstriction by A beta peptides, suggesting that the effects are partly mediated via a decrease in the nitric oxide/superoxide ratio. Enhancement of endothelin vasoconstriction is observed with A beta 1-40 and A beta 1-42, but not with A beta 25-35 even at 5 microM, again suggesting the mechanism of A beta vasoactivity is distinct from that of A beta cytotoxicity. These observations raise the possibility that A beta peptides in contact with the cerebrovasculature could result in vasoconstriction, hypoperfusion and oxygen free radical imbalance contributing to the neurodegeneration of AD.
Crawford
F
F
Department of Psychiatry, Roskamp Laboratories, University of South Florida, Tampa 33613, USA.
Suo
Z
Z
Fang
C
C
Sawar
A
A
Su
G
G
Arendash
G
G
Mullan
M
M
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D014700:Verapamil; D013482:Superoxide Dismutase