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The preferential β 3 ‐adrenoceptor agonist BRL 37344 increases force via β 1 ‐/β 2 ‐adrenoceptors and induces endothelial nitric oxide synthase via β 3 ‐adrenoceptors in human atrial myocardium
Author(s) -
Pott C,
Brixius K,
Bundkirchen A,
Bölck B,
Bloch W,
Steinritz D,
Mehlhorn U,
Schwinger R H G
Publication year - 2003
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 - 10.1038/sj.bjp.0705065
Subject(s) - enos , medicine , propranolol , endocrinology , contractility , isoprenaline , chemistry , inotrope , agonist , nitric oxide synthase , stimulation , nitric oxide , antagonist , ventricle , atrium (architecture) , chronotropic , receptor , heart rate , biology , blood pressure , atrial fibrillation
The present study investigated the effects of the preferential β 3 ‐AR agonist BRL 37344 (BRL) on force of contraction (FOC), Ca 2+ ‐transient and eNOS‐activity in human right atrial myocardium. 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 μ M ). BRL acted as a competitive antagonist towards isoprenaline and in binding experiments it was shown to have a distinct affinity towards β 1/2 ‐AR. In immunohistochemical experiments BRL (10 μ M ) increased detection of activated eNOS. This effect remained constant in the presence of propranolol (0.3 μ M ). BRL increased directly detected NO in DAF‐staining experiments. This increase was significantly smaller in the presence of the NO‐inhibitor L ‐NAME. The inotropic effects of BRL were not changed in the presence of L ‐NMA. These results suggest that the inotropic effects of BRL in human atrium are mediated via β 1/2 ‐AR, whereas the increase of atrial eNOS‐activity is due to β 3 ‐ adrenergic stimulation. This increase in eNOS‐activity did not influence atrial myocardial contractility. In conclusion, this study shows that β 3 ‐adrenergic stimulation is present in human atrium, but may not be functionally as significant as in the left ventricle.British Journal of Pharmacology (2003) 138 , 521–529. doi: 10.1038/sj.bjp.0705065