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 mu M) 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 mu M, 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.