Influence of drugs with affinity for α-adrenoceptors on noradrenaline release by potassium,tyramine and dimethylphenylpiperazinium

The influence of oxymetazoline and phentolamine on the overflow of noradrenaline evoked by potassium, tyramine and dimethylphenylpiperazinium (DMPP) was investigated in isolated perfused rabbit hearts.Oxymetazoline decreased, and phentolamine increased, the outflow of noradrenaline evoked by potassium. In hearts previously perfused with (?)-³H-noradrenaline, oxymetazoline reduced, and phentolamine enhanced, potassium-induced overflow of both ³H-noradrenaline and total tritium. These actions closely resemble previously described effects on noradrenaline overflow evoked by electrical stimulation of sympathetic nerves. At concentrations which modified the response to potassium, oxymetazoline and phentolamine did not influence the overflow evoked by tyramine. Both drugs diminished DMPP-induced overflow.It is concluded that oxymetazoline depresse noradrenaline release evoked by potassium or orthodromic action potentials through activation of neuronal α-adrenoceptors, followed by inhibition of electro-secretory coupling. Phentolamine blocks the analogous inhibitory effect of liberated noradrenaline and thus enhances release. The action of tyramine does not involve electro-secretory coupling and therefore is not changed. The influence of oxymetazoline and phentolamine on noradrenaline release by DMPP is not related to α-adrenoceptors.