Selective modulation of noradrenaline release by α2‐adrenoceptor blockade in the rat‐tail artery in vitro

Abstract

The effects of blocking alpha(2)-adrenoceptors on noradrenaline (NA) and adenosine 5'-triphosphate (ATP) release from postganglionic sympathetic nerves have been investigated in rat-tail artery in vitro. Continuous amperometry was used to measure NA release and intracellularly recorded excitatory junction potentials (e.j.p.'s) were used to measure ATP release. Application of the alpha(2)-adrenoceptor antagonist, idazoxan (1 microm), increased the amplitude of NA-induced oxidation currents evoked by trains of 10 stimuli at 1 and 10 Hz. In cells deep in the media, idazoxan (1 microm) had no effect on the amplitude of e.j.p.'s evoked by trains of 10 stimuli at 1 and 10 Hz. In cells close to the adventitial - medial border, idazoxan produced a small increase in the amplitude of e.j.p.'s evoked at the end of trains of 10 stimuli at 1 Hz. In tissues pretreated with the neuronal NA uptake inhibitor, desmethylimpramine (0.3 microm), idazoxan (1 microm) markedly increased the amplitude of e.j.p.'s in cells deep in the media. The alpha(2)-adrenoceptor agonist, clonidine (0.5 microm), produced similar reductions in the amplitudes of both NA-induced oxidation currents and e.j.p.'s evoked by 10 stimuli at 1 Hz. These effects of clonidine were reversed by the subsequent addition of idazoxan (1 microm). The release of both NA and ATP is inhibited to a similar extent by activation of prejunctional alpha(2)-adrenoceptors by clonidine. In contrast, endogenously released NA more markedly inhibits NA release. These findings provide further support for the differential modulation of NA and ATP release.