Evidence for noradrenergic-purinergic cotransmission in the hepatic artery of the rabbit.

1. Transmural electrical field stimulation produced a transient contraction of the isolated hepatic artery of the rabbit that was frequency-dependent up to 64 Hz. A contraction was rarely evoked at a stimulation frequency of less than 8 Hz and never at 4 Hz or less. All contractions were abolished in the presence of tetrodotoxin. 2. Neurogenic contractions were partially inhibited by prazosin. After desensitization of the P2X-purinoceptor with alpha, beta-methylene ATP, contractions in response to electrical stimulation were significantly reduced at all frequencies tested (4-64 Hz). In most cases, contractions were abolished by a combination of both drugs. 3. In vessels treated with 6-hydroxydopamine, no nerve-mediated contractile responses were observed. 4. In arteries from reserpine-treated rabbits, nerve stimulation evoked contractions that were resistant to prazosin. After desentization of the P2X-purinoceptor with alpha,beta-methylene ATP, no neurogenic contractile response remained. 5. The tissue contracted to exogenously applied noradrenaline and alpha,beta-methylene ATP. There was an increase in sensitivity to noradrenaline in 6-hydroxydopamine-treated vessels compared with control vessels, but no difference in potency to alpha,beta-methylene ATP was detected. The potency of noradrenaline and alpha,beta-methylene ATP was not significantly affected by reserpine treatment. 6. In control tissues, fluorescence histochemistry demonstrated the presence of noradrenergic nerve fibres. Noradrenaline-containing nerves were not observed in 6-hydroxydopamine-treated or reserpine-treated vessels. 7. It is concluded that noradrenaline and ATP are cotransmitters in the sympathetic nerves supplying the hepatic artery of the rabbit. In contrast to other vessels, the hepatic artery requires a relatively high frequency of stimulation to evoke contractions and the purinergic component is not frequency-dependent. The significance of this finding in terms of the physiological demands of blood flow to the liver are discussed.