Abstract
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 beta 1-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
greater than or equal to R-phenylisopropyl-adenosine greater than
N-ethylcarboxamidoadenosine greater than S-phenylisopropyl-adenosine)
suggests an adenosine A1-receptor mediated presynaptic inhibition
of noradrenaline release.
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