MP54-08 EFFECTS OF VIBEGRON, A NEW β3-ADRENOCEPTOR AGONIST, ON DETRUSOR OVERACTIVITY AND REMODELING IN A MOUSE MODEL OF SPINAL CORD INJURY (SCI)

Abstract

INTRODUCTION AND OBJECTIVE: Vibegron is a new β3-adrenoceptor agonist that was approved for the treatment of overreactive bladder (OAB) in Japan in 2018, and could potentially be used to treat patients with neurogenic bladder dysfunction due to SCI. Therefore, we examined the bladder activity and fibrotic and ischemic changes in the bladder of SCI mice with or without vibegron treatment. METHODS: Female C57BL/6N mice were used, and divided into three groups: A group of spinal cord intact mice; B group of SCI mice treated with vehicle; and C group of SCI mice treated with vibegron. SCI mice underwent Th8-9 spinal cord transection followed by oral administration of vehicle or vibegron (30 mg/kg/day) in the morning between 2 to 4 weeks after SCI. The bladder of SCI mice was emptied by abdominal compression once daily after SCI. We evaluated the urodynamic parameters using awake cystometry, the mRNA levels of fibrosis and ischemia-related molecules, and collagen and elastin levels of the bladder 4 weeks after SCI. RESULTS: The number of non-voiding contractions (NVCs) per voiding cycle was significantly lower in the C group than in the B group (Fig. 1A, B). The time required to induce the 1st NVC was significantly longer in the C group than in the B group. In molecular studies, mRNA expression of type 1 collagen, type 3 collagen, transforming growth factor-β1 (TGF-β1), and hypoxia inducible factor-1α (HIF-1α) were significantly higher in the B group than in A and C groups (Fig. 1C). Total collagen and total elastin were significantly higher in the B group than in the A group. CONCLUSIONS: Vibegron, a new β3-adrenoceptor agonist approved for OAB, reduced the number of NVCs, delayed the 1st NVC to appear, and improved the mRNA expression of type 1 collagen, type 3 collagen, TGF-β1 and HIF-1α although the protein level of collagen is not decreased yet at this stage of SCI (4 weeks). Vibegron would be effective for reducing SCI-induced neurogenic detrusor overactivity and tissue remodeling in the bladder.Source of Funding: DOD W81XWH-17-1-0403 KAKENHI for Early-Career Scientists (18K16751)