Effects of a new β3‐adrenoceptor agonist, vibegron, on neurogenic bladder dysfunction and remodeling in mice with spinal cord injury
Copyright policy )Effects of a new β3‐adrenoceptor agonist, vibegron, on neurogenic bladder dysfunction and remodeling in mice with spinal cord injury
AbstractAimsTo examine vibegron effects on lower urinary tract dysfunction (LUTD) in mice with spinal cord injury (SCI).MethodsFemale 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.ResultsNon‐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.ConclusionsVibegron 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.
- Kindai University Japan
- University of Pittsburgh United States
- Nara Medical University Japan
- University of Pennsylvania United States
Pyrrolidines, Urination, Adrenergic beta-3 Receptor Agonists, Pyrimidinones, Rats, Sprague-Dawley, Disease Models, Animal, Mice, Urodynamics, Treatment Outcome, Animals, Female, Urinary Bladder, Neurogenic, Spinal Cord Injuries
Pyrrolidines, Urination, Adrenergic beta-3 Receptor Agonists, Pyrimidinones, Rats, Sprague-Dawley, Disease Models, Animal, Mice, Urodynamics, Treatment Outcome, Animals, Female, Urinary Bladder, Neurogenic, Spinal Cord Injuries
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