Andrzej Wróbel1, Barbara Miziak2, Małgorzata Bańczerowska-Górska3, Aleksandra Szopa4, Anna Serefko4, Klaudia Stangel-Wójcikiewicz5, Piotr Czuczwar6, Marzena Laskowska7, Edyta Wlaźlak8, Jarosław Dudka9, Ewa Poleszak4. 1. Second Department of Gynecology, Medical University of Lublin, Lublin, Poland. 2. Department of Pathophysiology, Medical University of Lublin, Lublin, Poland. 3. Obstetrics and Gynaecology Ward, Gynaecological and Obstetrics Hospital in Wałbrzych, Wałbrzych, Poland. 4. Chair and Department of Applied Pharmacy, Medical University of Lublin, Lublin, Poland. 5. Gynecology and Oncology Department, Jagiellonian University Medical College St. M, Kraków, Poland. 6. Third Department of Gynecology, Medical University of Lublin, Lublin, Poland. 7. Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, Lublin, Poland. 8. First Department of Gynecology and Obstetrics, Clinic of Operative Gynecology and Gynecologic Oncology, Medical University of Lodz, Łódź, Poland. 9. Chair and Department of Toxicology, Medical University of Lublin, Lublin, Poland.
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.
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.
Authors: Łukasz Zapała; Kajetan Juszczak; Przemysław Adamczyk; Jan Adamowicz; Aleksander Ślusarczyk; Tomasz Kluz; Marcin Misiek; Artur Rogowski; Magdalena Emilia Grzybowska; Klaudia Stangel-Wójcikiewicz; Mikołaj Piotr Zaborowski; Ewa Poleszak; Piotr Radziszewski; Andrzej Wróbel Journal: Front Mol Biosci Date: 2022-06-21