The Vasoactivity of Aβ Peptides

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Abstract
We have demonstrated that freshly solubilized Aβ peptides can enhance vasoconstriction by phenylephrine or endothelin of isolated rat aorta. Concentrations of peptide producing these effects (100 nM—1 μM) 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 Aβ cell culture toxicity experiments. Pre‐treatment with SOD diminishes the enhancement of vasoconstriction by Aβ peptides, suggesting that the effects are partly mediated via a decrease in the nitric oxide/superoxide ratio. Enhancement of endothelin vasoconstriction is observed with Aβ1‐40 and Aβ1‐42, but not with Aβ25‐35 even at 5 μM, again suggesting the mechanism of Aβ vasoactivity is distinct from that of Aβ cytotoxicity. These observations raise the possibility that Aβ peptides in contact with the cerebrovasculature could result in vasoconstriction, hypoperfusion and oxygen free radical imbalance contributing to the neurodegeneration of AD.