MODULATION OF NORADRENALINE RELEASE FROM ISOLATED HUMAN ATRIAL APPENDAGES

Prejunctional modulation of noradrenaline release has been studied ext ensively in various experimental preparations. However, the presence a nd importance of prejunctional noradrenaline release modulation in hum an cardiac tissue is still unclear. In this study, we have used superf used human right atrial appendages excised from patients undergoing op en heart surgery. The tissues were cut into six pieces and incubated w ith [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 washe d 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 durin g which a field stimulation (2 ms pulses, 60 s, 50 mA, 5 Hz) was deliv ered at 10 and 45 min. The effect of the drugs on the stimulation-indu ced outflow of radioactivity was determined by adding them 20 min befo re the second stimulation, Each experiment was carried out with or wit hout desipramine (1 mu M) to study the influence of the reuptake block ade. Fenoterol (1-1000 nM), a beta(2)-adrenoceptor agonist, and angiot ensin II (1-1000 nM) significantly increased noradrenaline release in a concentration-dependent manner. The administration of arecaidine pro pargyl ester (0.03-3 mu M), a non-specific muscarinic receptor agonist , and propylnorapomorphine (0.1 nM-1 mu M), a DA(2)-dopaminergic agoni st, produced a concentration-dependent inhibition of the stimulation-i nduced outflow of radioactivity. The alpha(2)-adrenoceptor agonist, ox ymetazoline (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 recept ors in the human atrial appendage.