Adenosine As a Modulator of Sympathetic Nerve-stimulation-induced Release of Noradrenaline from the Isolated Rabbit Heart

The ability of adenosine to inhibit sympathetic nerve-stimulation-induced overflow of noradrenaline was studied in isolated rabbit hearts with intact sympathetic innervation. Noradrenaline in the heart effluents was measured by HPLC with electrochemical detection. The drugs used, adenosine, theophylline, and 8-parasulphophenyltheophylline, were administered via the perfusion fluid. Adenosine (1-100 microM) dose-dependently inhibited stimulation-evoked outflow of noradrenaline from the heart, by up to 47%: the inhibition was completely antagonized by theophylline (200 microM), and by 8-parasulphophenyltheophylline (100 microM). Neither theophylline nor 8-parasulphophenyltheophylline did per se affect basal or stimulation-evoked outflow of noradrenaline. Simultaneous infusion of adenosine (100 microM) and theophylline (200 microM) significantly increased the outflow of noradrenaline during nerve stimulation, by almost 40%. No such effect was observed by adenosine (100 microM) and 8-parasulphophenyltheophylline (100 microM), indicating that theophylline may facilitate transmitter release by an action dissociated from purinoceptor antagonism. It is concluded that (a) adenosine inhibits depolarization-induced liberation of sympathetic transmitter in the rabbit heart, (b) this inhibition is mediated by activation or purinoceptors, probably located on the presynaptic nerve terminals, and (c) brief periods of sympathetic stimulation in the normoxic heart does not release sufficient amounts of adenosine to cause significant inhibition of transmitter release.