Electrical field stimulation in cerebral and peripheral arteries: a critical evaluation of the contractile response

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.