ABSTRACT Objectives In this study, we aimed to investigate the impact of vibegron, a β 3 ‐adrenergic receptor agonist, on lower urinary tract dysfunction in a diabetic rat model. Methods Female rats were categorized into three groups: non‐diabetic controls (N), streptozotocin‐induced diabetic rats receiving vehicle (D), and diabetic rats treated with vibegron (DV). In the DV group, vibegron was administered orally at 30 mg/kg/day starting 7–8 weeks after diabetes induction. At 8 weeks post‐induction, voiding assays, urinary 8‐hydroxydeoxyguanosine (8‐OHdG) measurements, cystometry, and analysis of bladder mRNA expression levels of ischemia‐ and inflammatory‐related markers were performed. Results The 24‐h voiding assays showed that Groups D and DV had markedly higher urine volume, average voided volume, voiding frequency, and water intake compared to Group N. Urinary 8‐OHdG levels were markedly elevated in Group D than those in Groups N and DV. Group D also exhibited higher opening pressure and non‐voiding contractions. Intercontraction intervals, voided volume, post‐void residual volume, bladder capacity, and compliance were significantly increased, while voiding efficiency was markedly decreased in Groups D and DV compared to that in Group N. Bladder mRNA expression of hypoxia‐inducible factor‐1 alpha (Hif1a) , vascular endothelial growth factor A ( Vegfa ), transforming growth factor‐beta 1 ( Tgfb1 ), and tumor necrosis factor alpha ( Tnfa ) was upregulated in Group D compared with that in Groups N and DV. Conclusions These findings suggest that vibegron may be a promising therapeutic option for addressing detrusor overactivity, ischemia, and inflammation of the bladder associated with diabetes mellitus.
Gotoh et al. (Sun,) studied this question.