title: 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 alpha 2-adrenoceptor agonist, UK 14304 (0.1 mumol-1) significantly inhibited noradrenaline release, resulting in a S2/S1 ratio of 0.49 (0.40-0.59), and the a 2-adrenoceptor antagonist, yohimbine (1 mumol l-1) increased noradrenaline release (S2/S1 1.83 [1.43-2.35]) during normoxia. Both compounds were ineffective during anoxia. 4. Adenosine (30 mumol-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 beta 2-adrenoceptor agonist, terbutaline (1 mumol l-1) increased (1.53 [1.14-2.01]) and the beta-adrenoceptor antagonist, pindolol (1 mumol 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 mumol 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 mumol 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 alpha 2-adrenoceptors and adenosine receptors, as well as facilitatory beta 2-adrenoceptors and angiotensin II receptors regulating noradrenaline release under normoxic conditions. During anoxia the responses to alpha 2-adrenoceptors and adenosine receptor stimulation are lost, whereas facilitatory responses to beta 2-adrenoceptors and adenosine 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.
authors.affiliation: Medizinische Klinik, Technische Universtität München, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Münch
authors.forename: T
authors.initials: T
authors.lastname: Kurz
authors.forename: T
authors.initials: T
authors.lastname: Urlbauer
authors.forename: M
authors.initials: M
authors.lastname: Seyfarth
authors.forename: G
authors.initials: G
authors.lastname: Richardt
mesh_terms: D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D004558:Electric Stimulation; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D017661:Receptors, Presynaptic; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D013779:Tetrodotoxin; D000241:Adenosine; D009638:Norepinephrine