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Differential presynaptic modulation of noradrenaline release in human atrial tissue in normoxia and anoxia
Author(s) -
Münch Götz,
Kurz Thomas,
Urlbauer Thomas,
Seyfarth Melchior,
Richardt Gert
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15614.x
Subject(s) - pindolol , endocrinology , yohimbine , medicine , adenosine , chemistry , stimulation , antagonist , agonist , adrenergic , purinergic receptor , propranolol , receptor , biology
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 (S 2 ) was compared with release during a preceding control stimulation (S 1 ). The results were expressed as the geometric means and 95% confidence intervals of the S 2 /S 1 ratio. 3 . The α 2 ‐adrenoceptor agonist, UK 14304 (0.1 μmol 1 −1 ) significantly inhibited noradrenaline release, resulting in a S 2 /S 1 ratio of 0.49 (0.40‐0.59), and the α 2 ‐adrenoceptor antagonist, yohimbine (1 μmol 1 −1 ) increased noradrenaline release (S 2 /S 1 1.83 [1.43‐2.35]) during normoxia. Both compounds were ineffective during anoxia. 4 . Adenosine (30 μmol 1 −1 ) inhibited noradrenaline release with a S 2 /S 1 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 β 2 ‐adrenoceptor agonist, terbutaline (1 μmol 1 −1 ) increased (1.53 [1.14‐2.01]) and the β‐adrenoceptor antagonist, pindolol (1 μmol 1 −1 ) suppressed noradrenaline release (0.62 [0.49‐0.79]) under normoxic conditions. During anoxia, pindolol significantly inhibited noradrenaline release with a S 2 /S 1 ratio of 0.66 (0.51‐0.85), whereas terbutaline did not influence noradrenaline release. 6 . Angiotensin II (0.1 μmol 1 −1 ) enhanced noradrenaline release resulting in a S 2 /S 1 ratio of 1.44 (1.34‐1.54), while the angiotensin II antagonist, losartan (1 μmol 1 −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 S 2 /S 1 ratio of 0.60 (0.46‐0.77) during anoxia. 7 . In conclusion, human cardiac tissue possesses presynaptic inhibitory α 2 ‐adrenoceptors and adenosine receptors, as well as facilitatory β 2 ‐adrenoceptors and angiotensin II receptors regulating noradrenaline release under normoxic conditions. During anoxia the responses to α 2 ‐adrenoceptors and adenosine receptor stimulation are lost, whereas facilitatory responses to β 2 ‐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.