Hardebo J E, Hanko J, Kåhrstrom J, Owman C
J Auton Pharmacol. 1986 Jun;6(2):85-96. doi: 10.1111/j.1474-8673.1986.tb00634.x.
Electrical field stimulation with recording of isometric contraction in vitro was carried out on small circular segments of pial arteries, in comparison with peripheral arteries from several regions of rat, rabbit, cow, cat, dog and man. It was found that tetrodotoxin (TTX)-resistant contractions were obtained more readily in pial arteries of various species, including man, than in peripheral arteries of similar size. In fact, it was not possible to obtain a purely neurogenic response -- without a TTX-resistant change in tone -- in any pial vessels tested. The stimulation parameters that induced TTX-resistant contraction in pial arteries were similar to those weak parameters that could reveal a purely neurogenic response in certain other arteries, such as rabbit central ear artery and rabbit and feline mesenteric arteries. In these arteries, release of noradrenaline (NA) onto postjunctional alpha-adrenoreceptors was found to be fully responsible for the contraction. The contractile response could be considerably potentiated by blockade of neuronal and extraneuronal uptake, prejunctional alpha-receptor blockade, and 4-aminopyridine (4-AP)-induced enhancement of transmitter release. Addition of compounds to prevent oxidation of released NA (EDTA by its ability to bind metal ions, and ascorbic acid-glutathione, which prevents formation of free radicals) did not enhance the neurogenic response. However, not even under any of these conditions was it possible to reveal a purely neurogenic response in cerebral arteries. Only TTX-resistant contractions, likely to be due to direct smooth muscle activation, were obtained. The explanation may be morphological differences related to myogenic propagation, probably together with poorly sensitive alpha-adrenoreceptors, in these pial arteries. The situation was further complicated by the fading of the TTX-resistant contraction which often occurred upon repeated stimulation. Therefore, acceptance of partial blockade by TTX as a criterion for a neurogenic response in cerebral vessels, as by several previous investigators, may lead to misinterpretation of the true nature of the response. Hence, when studying neurogenic mechanisms in vitro in these arteries, parameters other than vascular tone should be recorded in conjunction with electrical field stimulation, such as registration of junction potentials and measurements of released transmitter.
对软脑膜动脉的小环形节段进行体外电场刺激并记录等长收缩，同时与来自大鼠、兔子、牛、猫、狗和人类几个区域的外周动脉进行比较。结果发现，与大小相似的外周动脉相比，包括人类在内的各种物种的软脑膜动脉更容易获得对河豚毒素（TTX）不敏感的收缩。事实上，在任何测试的软脑膜血管中，都不可能获得纯粹的神经源性反应——即没有TTX不敏感的张力变化。在软脑膜动脉中诱导TTX不敏感收缩的刺激参数与那些能在某些其他动脉（如兔中耳动脉以及兔和猫的肠系膜动脉）中揭示纯粹神经源性反应的微弱参数相似。在这些动脉中，去甲肾上腺素（NA）释放到节后α-肾上腺素能受体上被发现是收缩的完全原因。通过阻断神经元和非神经元摄取、节前α-受体阻断以及4-氨基吡啶（4-AP）诱导的递质释放增强，收缩反应可得到显著增强。添加防止释放的NA氧化的化合物（通过其结合金属离子的能力的乙二胺四乙酸以及防止自由基形成的抗坏血酸-谷胱甘肽）并没有增强神经源性反应。然而，即使在这些条件中的任何一种情况下，也不可能在脑动脉中揭示纯粹的神经源性反应。仅获得了可能由于直接平滑肌激活导致的TTX不敏感收缩。解释可能是这些软脑膜动脉中与肌源性传播相关的形态学差异，可能还伴有敏感性较差的α-肾上腺素能受体。由于TTX不敏感收缩在重复刺激时经常消退，情况进一步复杂化。因此，像之前几位研究者那样，将TTX部分阻断作为脑血管神经源性反应的标准，可能会导致对反应真实性质的误解。因此，在体外研究这些动脉的神经源性机制时，除了血管张力外，还应结合电场刺激记录其他参数，如连接电位的记录和释放递质的测量。
