Effects of dopamine β‐hydroxylase inhibition in pressure overload‐induced right ventricular failure
Abstract Activation of the sympathetic nervous system is observed in pulmonary arterial hypertension patients. This study investigates whether inhibiting the conversion of dopamine into noradrenaline by dopamine β‐hydroxylase (DβH) inhibition with BIA 21‐5337 improved right ventricular (RV) function...
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| Format: | Article |
| Language: | English |
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Wiley
2024-10-01
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| Series: | Pulmonary Circulation |
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| Online Access: | https://doi.org/10.1002/pul2.70008 |
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| author | Stine Andersen Julie Sørensen Axelsen Anders H. Nielsen‐Kudsk Janne Schwab Caroline D. Jensen Steffen Ringgaard Asger Andersen Rowan Smal Aida Llucià‐Valldeperas Frances Handoko de Man Bruno Igreja Nuno Pires |
| author_facet | Stine Andersen Julie Sørensen Axelsen Anders H. Nielsen‐Kudsk Janne Schwab Caroline D. Jensen Steffen Ringgaard Asger Andersen Rowan Smal Aida Llucià‐Valldeperas Frances Handoko de Man Bruno Igreja Nuno Pires |
| author_sort | Stine Andersen |
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| description | Abstract Activation of the sympathetic nervous system is observed in pulmonary arterial hypertension patients. This study investigates whether inhibiting the conversion of dopamine into noradrenaline by dopamine β‐hydroxylase (DβH) inhibition with BIA 21‐5337 improved right ventricular (RV) function or remodeling in pressure overload‐induced RV failure. RV failure was induced in male Wistar rats by pulmonary trunk banding (PTB). Two weeks after the procedure, PTB rats were randomized to vehicle (n = 8) or BIA 21‐5337 (n = 11) treatment. An additional PTB group treated with ivabradine (n = 11) was included to control for the potential heart rate‐reducing effects of BIA 21‐5337. A sham group (n = 6) received vehicle treatment. After 5 weeks of treatment, RV function was assessed by echocardiography, magnetic resonance imaging, and invasive pressure–volume measurements before rats were euthanized. RV myocardium was analyzed to evaluate RV remodeling. PTB caused a fourfold increase in RV afterload which led to RV dysfunction, remodeling, and failure. Treatment with BIA 21‐5337 reduced adrenal gland DβH activity and 24‐h urinary noradrenaline levels confirming relevant physiological response to the treatment. At end‐of‐study, there were no differences in RV function or RV remodeling between BIA 21‐5337 and vehicle‐treated rats. In conclusion, treatment with BIA 21‐5337 did not have any beneficial—nor adverse—effects on the development of RV failure after PTB despite reduced adrenal gland DβH activity. |
| format | Article |
| id | doaj-art-1a845d3aa4a44df9bd9813b10ea4dc75 |
| institution | Kabale University |
| issn | 2045-8940 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj-art-1a845d3aa4a44df9bd9813b10ea4dc752024-12-27T05:54:34ZengWileyPulmonary Circulation2045-89402024-10-01144n/an/a10.1002/pul2.70008Effects of dopamine β‐hydroxylase inhibition in pressure overload‐induced right ventricular failureStine Andersen0Julie Sørensen Axelsen1Anders H. Nielsen‐Kudsk2Janne Schwab3Caroline D. Jensen4Steffen Ringgaard5Asger Andersen6Rowan Smal7Aida Llucià‐Valldeperas8Frances Handoko de Man9Bruno Igreja10Nuno Pires11Department of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Clinical Medicine, MR Research Centre Aarhus University Aarhus DenmarkDepartment of Cardiology Aarhus University Hospital Aarhus DenmarkDepartment of Pulmonology Amsterdam University Medical Centre Amsterdam The NetherlandsDepartment of Pulmonology Amsterdam University Medical Centre Amsterdam The NetherlandsDepartment of Pulmonology Amsterdam University Medical Centre Amsterdam The NetherlandsDepartment of Research BIAL, Portela & Cª, S.A. Coronado S. Romão e S. Mamede PortugalDepartment of Research BIAL, Portela & Cª, S.A. Coronado S. Romão e S. Mamede PortugalAbstract Activation of the sympathetic nervous system is observed in pulmonary arterial hypertension patients. This study investigates whether inhibiting the conversion of dopamine into noradrenaline by dopamine β‐hydroxylase (DβH) inhibition with BIA 21‐5337 improved right ventricular (RV) function or remodeling in pressure overload‐induced RV failure. RV failure was induced in male Wistar rats by pulmonary trunk banding (PTB). Two weeks after the procedure, PTB rats were randomized to vehicle (n = 8) or BIA 21‐5337 (n = 11) treatment. An additional PTB group treated with ivabradine (n = 11) was included to control for the potential heart rate‐reducing effects of BIA 21‐5337. A sham group (n = 6) received vehicle treatment. After 5 weeks of treatment, RV function was assessed by echocardiography, magnetic resonance imaging, and invasive pressure–volume measurements before rats were euthanized. RV myocardium was analyzed to evaluate RV remodeling. PTB caused a fourfold increase in RV afterload which led to RV dysfunction, remodeling, and failure. Treatment with BIA 21‐5337 reduced adrenal gland DβH activity and 24‐h urinary noradrenaline levels confirming relevant physiological response to the treatment. At end‐of‐study, there were no differences in RV function or RV remodeling between BIA 21‐5337 and vehicle‐treated rats. In conclusion, treatment with BIA 21‐5337 did not have any beneficial—nor adverse—effects on the development of RV failure after PTB despite reduced adrenal gland DβH activity.https://doi.org/10.1002/pul2.70008animal studydopamine β‐hydroxylasenoradrenalineright heart failuresympathetic nervous system |
| spellingShingle | Stine Andersen Julie Sørensen Axelsen Anders H. Nielsen‐Kudsk Janne Schwab Caroline D. Jensen Steffen Ringgaard Asger Andersen Rowan Smal Aida Llucià‐Valldeperas Frances Handoko de Man Bruno Igreja Nuno Pires Effects of dopamine β‐hydroxylase inhibition in pressure overload‐induced right ventricular failure Pulmonary Circulation animal study dopamine β‐hydroxylase noradrenaline right heart failure sympathetic nervous system |
| title | Effects of dopamine β‐hydroxylase inhibition in pressure overload‐induced right ventricular failure |
| title_full | Effects of dopamine β‐hydroxylase inhibition in pressure overload‐induced right ventricular failure |
| title_fullStr | Effects of dopamine β‐hydroxylase inhibition in pressure overload‐induced right ventricular failure |
| title_full_unstemmed | Effects of dopamine β‐hydroxylase inhibition in pressure overload‐induced right ventricular failure |
| title_short | Effects of dopamine β‐hydroxylase inhibition in pressure overload‐induced right ventricular failure |
| title_sort | effects of dopamine β hydroxylase inhibition in pressure overload induced right ventricular failure |
| topic | animal study dopamine β‐hydroxylase noradrenaline right heart failure sympathetic nervous system |
| url | https://doi.org/10.1002/pul2.70008 |
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