Efficacy of vibegron, a novel β3‐adrenoreceptor agonist, for lower urinary tract dysfunction in mice with spinal cord injury

• Published in: International journal of urology 2021-10, Vol.28 (10), p.1068-1072
• Main Authors: Shimizu, Nobutaka, Gotoh, Daisuke, Nishimoto, Mitsuhisa, Hashimoto, Mamoru, Saito, Tetsuichi, Fujita, Kazutoshi, Hirayama, Akihide, Yoshimura, Naoki, Uemura, Hirotsugu
• Format: Article
• Language: English
• Subjects: Activating transcription factor 3; Adrenergic receptors; Agonists; Cytokines; Dorsal root ganglia; Inflammation; mice; mRNA; neurogenic lower urinary tract dysfunction; Nitric oxide; Nitric-oxide synthase; Oral administration; Polymerase chain reaction; Sensory neurons; Spinal cord injuries; spinal cord injury; Transcription factors; Transient receptor potential proteins; Urinary tract; Urination; urodynamics; Urogenital system; vibegron
• ISSN: 0919-8172; 1442-2042
• DOI: 10.1111/iju.14630

Objectives To investigate the effect of vibegron, a new clinically approved β3‐adrenoceptor agonist in lower urinary tract dysfunction in mice with spinal cord injury. Methods Investigators performed cystometry under awake conditions in 4‐week spinal cord injury female mice. Two weeks after spinal cord injury, saline or vibegron (30 mg/kg) was orally administered for 2 weeks prior to the urodynamic study. Investigators removed L6‐S1 dorsal root ganglia from the saline‐ or vibegron‐treated spinal cord injury mice as well as from saline‐treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase transcripts using real‐time polymerase chain reaction. Results In vibegron‐treated spinal cord injury mice, nonvoiding contractions during bladder filling, which were increased in spinal cord injury compared to spinal intact mice, were significantly decreased. Micturition pressure or voiding efficiency was not significantly increased in comparison to measurements in saline‐treated spinal cord injury mice. The expression of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase messenger RNA was increased in spinal cord injury mice compared to spinal intact mice, but significantly decreased after vibegron treatment. Conclusions Vibegron improves spinal cord injury‐induced detrusor overactivity in addition to significantly reducing C‐fiber afferent receptors such as transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, and inflammatory cytokines/markers, such as activating transcription factor 3 and inducible nitric oxide synthase, in spinal cord injury mice. Thus, vibegron might be effective in the treatment of storage lower urinary tract dysfunction induced by C‐fiber afferent activation after spinal cord injury.