Literature DB >> 27367752

Combinational effects of muscarinic receptor inhibition and β3-adrenoceptor stimulation on neurogenic bladder dysfunction in rats with spinal cord injury.

Naoki Wada1,2, Takahiro Shimizu1, Shun Takai1, Nobutaka Shimizu1, Pradeep Tyagi1, Hidehiro Kakizaki2, Naoki Yoshimura1.   

Abstract

AIMS: To investigate the effects of combined therapy with an anticholinergic agent and a β3-adrenoceptor agonist on bladder dysfunction and proliferation-related molecule expression in rats with spinal cord injury (SCI).
METHODS: The spinal cord was transected at the level of T8-9 in female Sprague-Dawley rats, which were divided into four groups; A: Vehicle, B: 10 mg/kg/day of oxybutynin, C: 10 mg/kg/day of mirabegron, and D: combined administration of oxybutynin and mirabegron. Drugs were administered by oral gavage from 2 to 4 weeks after spinal cord transection. We evaluated urodynamic parameters and bladder tissue remodeling factors.
RESULTS: Non-voiding contractions (NVCs) during the storage phase of cystometrograms tended to be decreased in all three treated groups with a significant reduction in group D versus A. Bladder compliance was improved, and intercontraction intervals, voided volume and bladder capacity were increased in group D. In all three treated groups (B-D), the expression of HIF1-α and TGF-β1 was decreased compared to group A. The expression of collagen-III and bFGF was decreased in groups B and D. The total bladder elastin level was increased in group D.
CONCLUSIONS: The combination therapy of an anticholinergic agent and a β3-adrenoceptor agonist elevated the bladder elastin level, reduced NVCs, and increased bladder compliance more effectively than the monotherapy in SCI rats. Thus, the combination therapy could be effective for the treatment of neurogenic bladder dysfunction including bladder remodeling. Neurourol. Urodynam. 36:1039-1045, 2017.
© 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Entities:  

Keywords:  anticholinergic; combination therapy; neurogenic bladder; spinal cord injury; β3-adrenoceptor

Mesh:

Substances:

Year:  2016        PMID: 27367752     DOI: 10.1002/nau.23066

Source DB:  PubMed          Journal:  Neurourol Urodyn        ISSN: 0733-2467            Impact factor:   2.696


  11 in total

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