Interaction between the release of adenosine and noradrenaline during sympathetic stimulation: A feed-back mechanism in rat heart

Interactions between the release of adenosine and noradrenaline were studied during sympathetic stimulation in rat heart perfused in situ. Cardiac sympathetic nerves were activated by electrical stimulation of the left cervicothoracic ganglion, and endogenous noradrenaline and adenosine were measured in the effluent from the heart. Following the onset of a continuous stimulation (6 min) a rise of heart rate was observed which was accompanied by the release of noradrenaline and adenosine. Specific blockade of adenosine receptors by 8-phenyltheophylline enhanced the stimulation induced release of noradrenaline suggesting an effective suppression of the noradrenaline release by endogenous adenosine. Heart rate and the release of adenosine were reduced by the β₁-adrenergic antagonist bisoprolol, while noradrenaline overflow increased. These results are compatible with the concept of a negative feed-back regulation of noradrenaline release by endogenous adenosine from the stimulated cardiomyocytes. In order to characterize the subtype of the presynaptic adenosine receptors involved, the inhibitory potency on stimulus induced noradrenaline release of metabolically stable adenosine agonists was tested. The order of potency (Cyclohexyladenosine ≥ R-phenylisopropyl-adenosine > N-ethylcarboxamidoadenosine > S-phenylisopropyl-adenosine) suggests an adenosine A₁-receptor mediated presynaptic inhibition of noradrenaline release.