The preferential β3‐adrenoceptor agonist BRL 37344 increases force viaβ1‐/β2‐adrenoceptors and induces endothelial nitric oxide synthase viaβ3 …
C Pott, K Brixius, A Bundkirchen, B Bölck… - British journal of …, 2003 - Wiley Online Library
C Pott, K Brixius, A Bundkirchen, B Bölck, W Bloch, D Steinritz, U Mehlhorn, RHG Schwinger
British journal of pharmacology, 2003•Wiley Online LibraryThe present study investigated the effects of the preferential β3‐AR agonist BRL 37344
(BRL) on force of contraction (FOC), Ca2+‐transient and eNOS‐activity in human right atrial
myocardium. 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 μm). BRL acted as
a competitive antagonist towards isoprenaline and in binding experiments it was shown to …
(BRL) on force of contraction (FOC), Ca2+‐transient and eNOS‐activity in human right atrial
myocardium. 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 μm). BRL acted as
a competitive antagonist towards isoprenaline and in binding experiments it was shown to …
- The present study investigated the effects of the preferential β3‐AR agonist BRL 37344 (BRL) on force of contraction (FOC), Ca2+‐transient and eNOS‐activity in human right atrial myocardium.
- 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 μM).
- BRL acted as a competitive antagonist towards isoprenaline and in binding experiments it was shown to have a distinct affinity towards β1/2‐AR.
- In immunohistochemical experiments BRL (10 μM) increased detection of activated eNOS. This effect remained constant in the presence of propranolol (0.3 μM).
- 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 β1/2‐AR, whereas the increase of atrial eNOS‐activity is due to β3‐ adrenergic stimulation. This increase in eNOS‐activity did not influence atrial myocardial contractility. In conclusion, this study shows that β3‐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
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