TY - JOUR
T1 - Effects of dopamine β-hydroxylase inhibition in pressure overload-induced right ventricular failure
AU - Andersen, Stine
AU - Axelsen, Julie Sørensen
AU - Nielsen-Kudsk, Anders H
AU - Schwab, Janne
AU - Jensen, Caroline D
AU - Ringgaard, Steffen
AU - Andersen, Asger
AU - Smal, Rowan
AU - Llucià-Valldeperas, Aida
AU - Handoko de Man, Frances
AU - Igreja, Bruno
AU - Pires, Nuno
N1 - © 2024 BIAL. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.
PY - 2024/10
Y1 - 2024/10
N2 - 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 (D
βH) 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 D
βH 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 D
βH activity.
AB - 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 (D
βH) 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 D
βH 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 D
βH activity.
KW - animal study
KW - dopamine β-hydroxylase
KW - noradrenaline
KW - right heart failure
KW - sympathetic nervous system
UR - http://www.scopus.com/inward/record.url?scp=85208954981&partnerID=8YFLogxK
U2 - 10.1002/pul2.70008
DO - 10.1002/pul2.70008
M3 - Journal article
C2 - 39539945
SN - 2045-8932
VL - 14
SP - e70008
JO - Pulmonary Circulation
JF - Pulmonary Circulation
IS - 4
M1 - e70008
ER -