Crawford F, Suo Z, Fang C, Sawar A, Su G, Arendash G, Mullan M
Department of Psychiatry, Roskamp Laboratories, University of South Florida, Tampa 33613, USA.
Ann N Y Acad Sci. 1997 Sep 26;826:35-46. doi: 10.1111/j.1749-6632.1997.tb48459.x.
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.
我们已经证明，新溶解的Aβ肽可增强苯肾上腺素或内皮素对离体大鼠主动脉的血管收缩作用。产生这些作用的肽浓度（100 nM - 1 μM）远低于培养中对内皮细胞产生毒性所需的浓度，且作用迅速，不像Aβ细胞培养毒性实验那样需要长时间聚集。用超氧化物歧化酶（SOD）预处理可减弱Aβ肽对血管收缩的增强作用，这表明这些作用部分是通过一氧化氮/超氧化物比例的降低介导的。Aβ1 - 40和Aβ1 - 42可增强内皮素的血管收缩作用，但即使在5 μM时，Aβ25 - 35也无此作用，这再次表明Aβ血管活性的机制与Aβ细胞毒性的机制不同。这些观察结果提示，与脑血管系统接触的Aβ肽可能导致血管收缩、灌注不足和氧自由基失衡，从而促成阿尔茨海默病（AD）的神经退行性变。
