Modulation of noradrenaline release from isolated human atrial appendages

Prejunctional modulation of noradrenaline release has been studied extensively in various experimental preparations. However, the presence and importance of prejunctional noradrenaline release modulation in human cardiac tissue is still unclear. In this study, we have used superfused human right atrial appendages excised from patients undergoing open heart surgery. The tissues were cut into six pieces and incubated with [H-3]noradrenaline (4 mu Ci/ml, 0.2 mu M) for 30 min at 37 degrees C. The tissues were then inserted into a suprafusion system and washed for 75 min with a Krebs-Henseleit solution at a rate of 0.4 ml/min. The experimental protocol consisted of a 60-min perfusion period during which a field stimulation (2 ms pulses, 60 s, 50 mA, 5 Hz) was delivered at 10 and 45 min. The effect of the drugs on the stimulation-induced outflow of radioactivity was determined by adding them 20 min before the second stimulation, Each experiment was carried out with or without desipramine (1 mu M) to study the influence of the reuptake blockade. Fenoterol (1-1000 nM), a beta(2)-adrenoceptor agonist, and angiotensin II (1-1000 nM) significantly increased noradrenaline release in a concentration-dependent manner. The administration of arecaidine propargyl ester (0.03-3 mu M), a non-specific muscarinic receptor agonist, and propylnorapomorphine (0.1 nM-1 mu M), a DA(2)-dopaminergic agonist, produced a concentration-dependent inhibition of the stimulation-induced outflow of radioactivity. The alpha(2)-adrenoceptor agonist, oxymetazoline (1 mu M), inhibited noradrenaline release at a stimulation frequency of 2 Hz, but not at 5 and 10 Hz. The alpha(2)-adrenoceptor antagonist, idazoxan (1 mu M), significantly increased the release of noradrenaline at 2 and 5 Hz but not at 10 Hz. The results obtained in the present study demonstrated the presence of the facilitatory beta(2)-adrenoceptor and angiotensin II receptor as well as the presence of inhibitory alpha(2)-adrenoceptor, muscarinic and DA(2)-dopamine receptors in the human atrial appendage.