The contributions of noradrenaline and ATP to the responses of the rabbit central ear artery to sympathetic nerve stimulation depend on the parameters of stimulation

Abstract

The possibility that ATP and noradrenaline act as cotransmitters from sympathetic perivascular nerves was studied in the isolated rabbit central ear artery. Electrical stimulation of the perivascular nerves for either 1 s, or continuously until a maximum response was reached, produced frequency-dependent contractions that were sensitive to tetrodotoxin and guanethidine. Contractions to continuous stimulation were significantly greater than those to a 1 s train of stimulation. Prazosin (10(-6) M) significantly reduced, but did not abolish, all neurogenic contractions such that contractions to both a 1 s train and to continuous stimulation were now of a similar magnitude. A higher concentration of prazosin (10(-5) M) had no additional inhibitory effect on neurogenic contractions even though it further significantly inhibited contractions to exogenous noradrenaline. The greatest resistance to alpha-adrenoceptor blockade was seen at low frequencies. Desensitisation of the postjunctional P2-purinoceptor by repeated administration of alpha, beta-methylene ATP inhibited the non-adrenergic neurogenic contractions and contractions to exogenous ATP, but had no effect on contractions to exogenous noradrenaline. It is concluded that ATP and noradrenaline are excitatory cotransmitters from sympathetic perivascular nerves innervating the rabbit central ear artery. The relative contribution of each compound to neurogenic contractions of the ear artery is highly dependent on the parameters of stimulation used. Short pulse bursts (1 s) at low frequency (2-5 Hz) favour the prazosin-resistant (purinergic) component of the response.