Effects of a new β3-adrenoceptor agonist, vibegron, on neurogenic bladder dysfunction and remodeling in mice with spinal cord injury

  • Neurourol Urodyn. 2020 Nov;39(8):2120-2127. doi: 10.1002/nau.24486.
Daisuke Gotoh  1  2 ,  Nobutaka Shimizu  1  3 ,  Naoki Wada  1 ,  Katsumi Kadekawa  1 ,  Tetsuichi Saito  1 ,  Shinsuke Mizoguchi  1 ,  Yosuke Morizawa  2 ,  Shunta Hori  2 ,  Makito Miyake  2 ,  Kazumasa Torimoto  2 ,  William C de Groat  4 ,  Kiyohide Fujimoto  2 ,  Naoki Yoshimura  1  4
Affiliations
  • 1. Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • 2. Department of Urology, Nara Medical University, Kashihara, Japan.
  • 3. Department of Urology, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan.
  • 4. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pennsylvania.
PMID: 32816344 DOI: 10.1002/nau.24486
Abstract

Aims: To examine vibegron effects on lower urinary tract dysfunction (LUTD) in mice with spinal cord injury (SCI).

Methods: Female mice underwent Th8-9 spinal cord transection and were orally administered vehicle or vibegron after SCI. We evaluated urodynamic parameters at 4 weeks after SCI with or without vibegron. Fibrosis- and ischemia-related messenger RNA (mRNA) and protein levels of Collagen and elastin were measured in bladders of vehicle- and vibegron-treated SCI mice, and spinal intact mice.

Results: Non-voiding contractions (NVCs) were significantly fewer (15.3 ± 8.9 vs 29.7 ± 11.4 contractions; P < .05) and the time to the first NVC was significantly longer (1488.0 ± 409.5 vs 782.7 ± 399.7 seconds; P < .01) in vibegron-treated SCI mice vs vehicle-treated SCI mice. mRNAs levels of Collagen types 1 and 3, transforming growth factor-β1 (TGF-β1), and hypoxia-inducible factor-1α (HIF-1α) were significantly upregulated in vehicle-treated SCI mice compared with spinal intact and vibegron-treated SCI mice (Col 1: 3.5 vs 1.0 and 2.0-fold; P < .01 and P < .05, Col 3: 2.1 vs 1.0 and 1.2-fold; P < .01 and P < .05, TGF-β1: 1.2 vs 1.0 and 0.9-fold; P < .05 and P < .05, HIF-1α: 1.4 vs 1.0 and 1.0-fold; P < .05 and P < .01). Total Collagen and elastin protein levels in vehicle- and vibegron-treated SCI mice did not differ.

Conclusions: Vibegron reduced NVCs, delayed the first NVC, and improved Collagen types 1 and 3, TGF-β1, and HIF-1α mRNA expression in SCI mice. Vibegron might be effective for SCI-induced LUTD.

Keywords
detrusor overactivity; mice; spinal cord injury; urodynamics; vibegron.
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