The preferential beta3-adrenoceptor agonist BRL 37344 increases force via beta1-/beta2-adrenoceptors and induces endothelial nitric oxide synthase via beta3-adrenoceptors in human atrial myocardium

C Pott, K Brixius, A Bundkirchen, B Bölck, W Bloch, D Steinritz, U Mehlhorn, R H G Schwinger

Publication: Contribution to journalJournal articlesResearchpeer-review

Abstract

1 The present study investigated the effects of the preferential beta(3)-AR agonist BRL 37344 (BRL) on force of contraction (FOC), Ca(2+)-transient and eNOS-activity in human right atrial myocardium. 2 BRL concentration-dependently caused an increase in FOC that was paralleled by an increase in Ca(2+)-transient and a shortening of time to half peak relaxation (T0.5T). These effects were abolished in the presence of propranolol (0.3 micro M). 3 BRL acted as a competitive antagonist towards isoprenaline and in binding experiments it was shown to have a distinct affinity towards beta(1/2)-AR. 4 In immunohistochemical experiments BRL (10 micro M) increased detection of activated eNOS. This effect remained constant in the presence of propranolol (0.3 micro M). 5 BRL increased directly detected NO in DAF-staining experiments. This increase was significantly smaller in the presence of the NO-inhibitor L-NAME. 6 The inotropic effects of BRL were not changed in the presence of L-NMA. 7 These results suggest that the inotropic effects of BRL in human atrium are mediated via beta(1/2)-AR, whereas the increase of atrial eNOS-activity is due to beta(3)- adrenergic stimulation. This increase in eNOS-activity did not influence atrial myocardial contractility. In conclusion, this study shows that beta(3)-adrenergic stimulation is present in human atrium, but may not be functionally as significant as in the left ventricle.

Original languageEnglish
JournalBritish journal of pharmacology
Volume138
Issue number3
Pages (from-to)521-9
Number of pages9
ISSN0007-1188
DOIs
Publication statusPublished - 01.02.2003

Research areas and keywords

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Aged
  • Calcium
  • Dose-Response Relationship, Drug
  • Enzyme Induction
  • Ethanolamines
  • Female
  • Fluorometry
  • Heart Atria
  • Humans
  • Immunohistochemistry
  • Male
  • Myocardium
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Propranolol
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-3

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