Effects of the inhibition of noradrenaline uptake and synthesis on the maintenance of the response to continuous nerve stimulation in the central artery of the rabbit ear.

1. The central artery of the rabbit ear was perfused through its lumen in vitro, with a constant pressure technique, and stimulated continuously via its periarterial sympathetic nerves at the physiological frequency of 5 Hz.2. The vasoconstrictor response, which led initially to an almost complete cessation of intraluminal flow, deteriorated steadily over a period of hours. The involvement of presynaptic mechanisms in this effect was indicated by the finding that noradrenaline, administered extraluminally, produced a similar response before the onset of continuous stimulation and at a late stage when the constriction had decreased markedly. In addition, the noradrenaline precursor DOPA, restored the depressed responses towards their original values, indicating that failure involved depletion of mediator for release.3. Responses to continuous stimulation declined significantly faster after inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine. However, inhibition of the uptake of noradrenaline with cocaine did not enhance the decline of the response, even when the sensitization produced by the compound was taken into account.4. It is concluded that synthesis, along with the mobilization of stored mediator, rather than uptake and re-use of noradrenaline maintain the effector response in the central artery of the rabbit ear stimulated continuously at a frequency within the physiological range.