Differential presynaptic modulation of noradrenaline release in human atrial tissue in normoxia and anoxia

Abstract

1. Presynaptic modulation of noradrenaline release in human atrial tissue specimens was investigated under normoxic and anoxic conditions. 2. Noradrenaline release was induced by electrical stimulation and release during experimental intervention (S2) was compared with release during a preceding control stimulation (S1). The results were expressed as the geometric means and 95% confidence intervals of the S2/S1 ratio. 3. The α2-adrenoceptor agonist, UK 14304 (0.1 μmol l-1) significantly inhibited noradrenaline release, resulting in a S2/S1 ratio of 0.49 (0.40-0.59), and the α2-adrenoceptor antagonist, yohimbine (1 μmol l-1) increased noradrenaline release (S2/S1 1.83 [1.43 -2.35]) during normoxia. Both compounds were ineffective during anoxia. 4. Adenosine (30 μmol l-1) inhibited noradrenaline release with a S2/S1 ratio of 0.54 (0.42-0.66). The adenosine antagonist, 8-phenyltheophylline, alone had no effect during normoxia. During anoxia, neither adenosine nor 8-phenyltheophylline altered noradrenaline release. 5. The β2-adrenoceptor agonist, terbutaline (1 μmol l-1) increased (1.53 [1.14-2.01]) and the β-adrenoceptor antagonist, pindolol (1 μmol l-1) suppressed noradrenaline release (0.62 [0.49-0.79]) under normoxic conditions. During anoxia, pindolol significantly inhibited noradrenaline release with a S2/S1 ratio of 0.66 (0.51-0.85), whereas terbutaline did not influence noradrenaline release. 6. Angiotensin II (0.1 μmol l-1) enhanced noradrenaline release resulting in a S2/S1 ratio of 1.44 (1.34-1.54), while the angiotensin II antagonist, losartan (1 μmol l-1) had no effect on noradrenaline release during normoxia. Conversely, angiotensin II did not increase noradrenaline release and losartan significantly inhibited noradrenaline release to a S2/S1 ratio of 0.60 (0.46-0.77) during anoxia. 7. In conclusion, human cardiac tissue possesses presynaptic inhibitory α2-adrenoceptors and adenosine receptors, as well as facilitatory β2-adrenoceptors and angiotensin II receptors regulating noradrenaline release under normoxic conditions. During anoxia the responses to α2-adrenoceptors and adenosine receptor stimulation are lost, whereas facilitatory responses to β2-adrenoceptors and angiotensin II receptor stimulation are maintained and these receptors appear to be maximally stimulated. This differential presynaptic modulation in anoxia may contribute to enhanced sympathetic activity in ischaemia.