Adrenaline hypothesis: effect of formoterol on noradrenaline release

Summary 1 Originally, the so‐called `adrenaline hypothesis' related the release of noradrenaline (NA) to stimulation of presynaptic β2‐receptors in nerve endings; now it confers a possible role to adrenaline taken up then released by nerves endings. It represents a potentially useful therapeutic pathway. The present study aims to investigate the effects of formoterol, a highly selective β2‐adrenoceptor agonist. 2 It was carried out in freely moving rats, the isotope dilution technique being used to measure the NA spill over rate (NA‐SOR) and metabolic clearance rate (MCR). 3 A series of three results are reported. (a) When compared with adrenaline on equimolar basis, formoterol (2.3 μg kg−1 min−1) increased NA‐SOR while mean arterial blood pressure was decreased and heart rate increased. Thus, it was difficult to separate a direct presynaptic effect from indirect baroreflex‐dependent activation of the sympathetic system. (b) When formoterol was infused at 1 ng kg−1 min−1, a dose empirically defined to induce no haemodynamic effect, NA‐SOR was significantly increased, while NA‐MCR remained unchanged. (c) The NA‐SOR response to formoterol was not amplified by the presynaptic α2‐adrenoceptor blocker, yohimbine, in contrast to the NA‐SOR response to adrenaline. 4 In conclusion, formoterol, a β2‐adrenoceptor agonist, is shown to increase the release and plasma concentration of NA while its clearance was not changed.