Pathophysiological studies of overactive bladder and bladder motor dysfunction in a rat model of metabolic syndrome

Wei Chia Lee, Yao Chi Chuang, Po Hui Chiang, Chiang-Ting Chien, Hong Jeng Yu, Chia Ching Wu

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Purpose: We studied bladder motor dysfunction and searched for markers of neurogenic and myogenic alterations among fructose fed rats with or without abnormal voiding behavior. Materials and Methods: Female Wistar rats were fed with a fructose rich diet (60%) or a normal diet for 6 months. Based on cystometry and voiding behavior the fructose fed rats were divided into 3 groups, including a group with normal detrusor function with normal micturition frequency, a group with detrusor overactivity with increased micturition frequency and a group with acontractile detrusor with increased micturition frequency. Denuded bladder tissues were obtained to assess in vitro detrusor contractility, postsynaptic receptors, smoothelin, nitrosative products and the intrinsic pathway of apoptosis. Results: Fructose fed rats with abnormal voiding behavior had obvious neurogenic and myogenic alterations, including increased expression of postsynaptic receptors, dysregulation of smoothelin and decreased expression of Bcl-2 with a subsequent increase in apoptotic cells in the bladder stroma, causing decreased carbachol induced contractility. Rats with detrusor overactivity were also insulted by nitrosative stress associated with nitrotyrosine up-regulation in the bladder tissue. Up-regulation of M 2 and M3-muscarinic receptors, and P2X1 receptors appeared to be generalized alterations of fructose fed rats and not exclusive to those with detrusor overactivity. Conclusions: Up-regulation of postsynaptic receptors and dysregulation of smoothelin contribute to overactive bladder symptoms in rats with metabolic syndrome. Nitrosative stress and decreased Bcl-2 expression lead to bladder muscle cell loss via the intrinsic pathway of apoptosis, which may further deteriorate bladder function.

Original languageEnglish
Pages (from-to)318-325
Number of pages8
JournalJournal of Urology
Volume186
Issue number1
DOIs
Publication statusPublished - 2011 Jul 1

Keywords

  • fructose
  • insulin resistance
  • metabolic syndrome X
  • overactive
  • urinary bladder

ASJC Scopus subject areas

  • Urology

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