Combined treatment with a ß3 -adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats.
Neurourol Urodyn
; 36(4): 1026-1033, 2017 04.
Article
en En
| MEDLINE
| ID: mdl-27367573
ABSTRACT
AIMS:
This study determined if combined treatment with the muscarinic receptor (MR) antagonist solifenacin and the ß3 -adrenergic receptor (AR) agonist mirabegron could inhibit detrusor overactivity induced by cold stress in spontaneously hypertensive rats (SHRs).METHODS:
Thirty-two female 10-week-old SHRs were fed an 8% NaCl-supplemented diet for 4 weeks. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then intravenously administered vehicle, 0.1 mg/kg solifenacin alone, 0.1 mg/kg mirabegron alone, or the combination of 0.1 mg/kg mirabegron and 0.1 mg/kg solifenacin (n = 8 each group). Five minutes later, the treated rats were exposed to low temperature (LT, 4 ± 2°C) for 40 min. Finally, the rats were returned to RT. After the cystometric investigations, the ß3 -ARs and M3 -MRs expressed within the urinary bladders were analyzed.RESULTS:
Just after transfer from RT to LT, vehicle-, solifenacin-, and mirabegron-treated SHRs exhibited detrusor overactivity that significantly decreased voiding interval and bladder capacity. However, treatment with the combination of solifenacin and mirabegron partially inhibited the cold stress-induced detrusor overactivity patterns. The decreases of voiding interval and bladder capacity in the combination-treated rats were significantly inhibited compared to other groups. Within the urinary bladders, there were no differences between expression levels of M3 -MR and ß3 -AR mRNA. The tissue distribution of M3 -MRs was similar to that of the ß3 -ARs.CONCLUSIONS:
This study suggested that the combination of solifenacin and mirabegron act synergistically to inhibit the cold stress-induced detrusor overactivity in SHRs. Neurourol. Urodynam. 361026-1033, 2017. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Tiazoles
/
Vejiga Urinaria
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Antagonistas Muscarínicos
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Vejiga Urinaria Hiperactiva
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Agonistas de Receptores Adrenérgicos beta 3
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Succinato de Solifenacina
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Acetanilidas
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Neurourol Urodyn
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón