The preferential β3-adrenoceptor agonist BRL 37344 increases force via β1-/β2-adrenoceptors and induces endothelial nitric oxide synthase via β3-adrenoceptors in human atrial myocardium

1 The present study investigated the effects of the preferential beta(3)-AR agonist BRL 37344 (BRL) on force of contraction (FOC), Ca2+-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 Ca2+-transient and a shortening of time to half peak relaxation (T0.5T). These effects were abolished in the presence of propranolol (0.3 muM). 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 muM) increased detection of activated eNOS. This effect remained constant in the presence of propranolol (0.3 muM). 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.