Parnavelas J G, Kelly W, Burnstock G
Nature. 1985;316(6030):724-5. doi: 10.1038/316724a0.
Furchgott and Zawadski have shown that acetylcholine (ACh) does not act directly on the smooth muscle of blood vessel walls, but rather via receptors on the endothelial cells lining the lumen, to release an endothelium-derived relaxing factor (EDRF). As it is very unlikely that neurotransmitter released from the periarterial nerves, which are confined to the adventitial-medial border, diffuses all the way through the medial muscle coat before acting on endothelial cells to release EDRF to produce vasodilatation, this discovery has been regarded as an indication of a pathophysiological mechanism, rather than a physiological one (see refs 2, 3). ACh is rapidly degraded in the blood by acetylcholinesterase, so that ACh must be released locally to be effective on endothelial cells. Here we demonstrate the immunocytochemical localization of choline acetyltransferase in endothelial cells of small brain vessels, which is consistent with the view that the ACh originates from endothelial cells that can synthesize and store it. We suggest that release of ACh following damage to endothelial cells during ischaemia contributes to a pathophysiological mechanism of vasodilation which protects that segment of vessel from further damage as well as brain cells from hypoxia.
弗奇戈特和扎瓦茨基已证明，乙酰胆碱（ACh）并非直接作用于血管壁的平滑肌，而是通过衬于管腔的内皮细胞上的受体，释放一种内皮衍生舒张因子（EDRF）。由于局限于外膜 - 中膜边界的动脉周围神经释放的神经递质极不可能在作用于内皮细胞释放EDRF以产生血管舒张之前，一路扩散穿过中层肌层，所以这一发现被视为一种病理生理机制的指征，而非生理机制（见参考文献2、3）。ACh在血液中会被乙酰胆碱酯酶迅速降解，因此ACh必须在局部释放才能对内皮细胞起作用。在此，我们展示了胆碱乙酰转移酶在脑小血管内皮细胞中的免疫细胞化学定位，这与ACh源自能够合成并储存它的内皮细胞这一观点相符。我们认为，缺血期间内皮细胞受损后ACh的释放促成了血管舒张的病理生理机制，该机制可保护那段血管免受进一步损伤，并保护脑细胞免受缺氧影响。
