Pharmacologic and molecular characterization of underactive bladder induced by lumbar canal stenosis

Hung Jen Wang, Pradeep Tyagi, Yao Chi Chuang*, Naoki Yoshimura, Chao Cheng Huang, Michael B. Chancellor

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

8 Scopus citations

Abstract

Objective To investigate the voiding function in a rat model of lumbar canal stenosis (LCS) using pharmacologic and molecular approaches. Methods Sixty-one female Sprague-Dawley rats were broadly split into a sham and an LCS group. A hole was surgically drilled in the L5-L6 epidural space and filled with a rectangular piece of silicone rubber. Metabolic cage study at week 2 and continuous cystometry (CMG) under urethane anesthesia at weeks 2 and 4 were performed. During CMG, prostaglandin E2 or sulprostone, an prostaglandin E receptor 1 and prostaglandin E receptor 3 agonist was administered locally and intravenously, respectively, and the bladder was then harvested for histology and Western blot. Results Compared with sham, the LCS group showed dribbling urination and progressive increase in bladder size. CMG under urethane anesthesia in the LCS group was marked by overflow incontinence and acontractile bladder. Administration of intravesical prostaglandin E2 (200 μM) or intravenous sulprostone (0.1 mg/kg) in the sham group induced bladder overactivity, but decreased the compliance and failed to restore the bladder emptying function in the LCS group. The LCS group showed edematous changes and muscle thinning at week 2, which were partially restored by week 4. Histologic changes were accompanied by downregulation of agrin protein (64.0%) at week 2 and upregulation of M2 receptor (65.4%) at week 4. Expression of M3, protein gene product 9.5, and nerve growth factor did not differ between groups. Conclusion LCS-induced underactive bladder is associated with altered expression of agrin and M2 receptor. The underactive bladder model is clinically relevant, and the findings indicate potential molecular targets for new therapies.

Original languageEnglish
Pages (from-to)1284-1290
Number of pages7
JournalUrology
Volume85
Issue number6
DOIs
StatePublished - 01 06 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

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