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The influence of nebivolol on the activity of BRL 37344 — the β3‐adrenergic receptor agonist, in the animal model of detrusor overactivity

2019; Wiley; Volume: 38; Issue: 5 Linguagem: Inglês

10.1002/nau.23993

1520-6777

Andrzej Wróbel, Barbara Miziak, Małgorzata Bańczerowska‐Górska, Aleksandra Szopa, Anna Serefko, Klaudia Stangel‐Wójcikiewicz, Piotr Czuczwar, Marzena Laskowska, Edyta Wlaźlak, Jarosław Dudka, Ewa Poleszak,

Heart Rate Variability and Autonomic Control

Abstract Aims The cardiotoxic effects of antimuscarinics constitute a significant restriction in their application in elderly people. Overactive bladder syndrome pharmacotherapy using compounds with cardioprotective properties would seem an ideal solution. The main goal of the study was to assess the impacts of nebivolol (NEB) on the activity of BRL 37344 — β3‐adrenergic receptor (β3AR) agonist, in the animal model of detrusor overactivity. As both these substances can impact on the cardiovascular system, their effect on the parameters of this system and diuresis was also examined. Methods Retinyl acetate (RA; 0.75%) solution was used to induce detrusor overactivity in female Wistar rats. BRL and/or NEB were administered intra‐arterially during cystometry in a single dose (2.5 or 5, 0.05 or 0.1 mg/kg, respectively). In addition, a 24 hours measurement of heart rate, blood pressure, and urine production was carried out. Results NEB (0.05 mg/kg) and BRL (2.5 mg/kg) monotherapy proved to have no influence on the cystometric parameters of animals with RA‐induced detrusor overactivity. NEB at 0.1 mg/kg resulted in a drop in the detrusor overactivity index, similarly to BRL at 5 mg/kg. Coadministration of NEB and BRL, both at ineffective doses, decreased the detrusor overactivity index and ameliorated the nonvoiding contractions. β3AR stimulation proved to induce tachycardia and hypertension. NEB at 0.05 mg/kg proved to ameliorate detrusor overactivity and have preventive properties against adverse cardiovascular effects of the β3AR agonist. Conclusions The combined application of the β3AR agonist and NEB may improve detrusor overactivity without affecting the heart rate, blood pressure, and urine production.