Ning Li1, Honglin Ding1,2, Zizheng Li1, Yili Liu3, Ping Wang1. 1. Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China. 2. Department of Urology, Affiliated Hospital, Chifeng University, 42 Wangfu Street, Chifeng, Neimeng, China. 3. Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China. air-nick@163.com.
Abstract
PURPOSE: Obesity usually induces overactive bladder (OAB) associated with detrusor overactivity, which is related to increased contractility of the detrusor smooth muscle (DSM). Small-conductance Ca2+-activated K+ (SK) channels play a constitutive role in the regulation of DSM contractility. However, the role of SK channels in the DSM changes in obesity-related OAB is still unknown. Here, we tested the hypothesis that obesity-related OAB is associated with reduced expression and activity of SK channels in DSM and that SK channels activation is a potential treatment for OAB. METHODS: Female Sprague-Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) and weighed after 12 weeks. Urodynamic studies, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and isometric tension recording were performed. RESULTS: Increased average body weights and urodynamically demonstrated OAB were observed in HFD rats. qRT-PCR experiments revealed a decrease in the mRNA expression level of SK channel in DSM tissue of the HFD rats. Isometric tension recordings indicated an attenuated relaxation effect of NS309 on the spontaneous phasic and electrical field stimulation-induced contractions that occurred via SK channel activation in HFD DSM strips. CONCLUSIONS: Reduced expression and activity of SK channels in the DSM contribute to obesity-related OAB, indicating that SK channels are a potential therapeutic target for OAB.
PURPOSE:Obesity usually induces overactive bladder (OAB) associated with detrusor overactivity, which is related to increased contractility of the detrusor smooth muscle (DSM). Small-conductance Ca2+-activated K+ (SK) channels play a constitutive role in the regulation of DSM contractility. However, the role of SK channels in the DSM changes in obesity-related OAB is still unknown. Here, we tested the hypothesis that obesity-related OAB is associated with reduced expression and activity of SK channels in DSM and that SK channels activation is a potential treatment for OAB. METHODS: Female Sprague-Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) and weighed after 12 weeks. Urodynamic studies, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and isometric tension recording were performed. RESULTS: Increased average body weights and urodynamically demonstrated OAB were observed in HFD rats. qRT-PCR experiments revealed a decrease in the mRNA expression level of SK channel in DSM tissue of the HFD rats. Isometric tension recordings indicated an attenuated relaxation effect of NS309 on the spontaneous phasic and electrical field stimulation-induced contractions that occurred via SK channel activation in HFD DSM strips. CONCLUSIONS: Reduced expression and activity of SK channels in the DSM contribute to obesity-related OAB, indicating that SK channels are a potential therapeutic target for OAB.
Authors: Steven A Buckner; Ivan Milicic; Anthony V Daza; Michael J Coghlan; Murali Gopalakrishnan Journal: Br J Pharmacol Date: 2002-02 Impact factor: 8.739
Authors: Michael E DiSanto; Raimund Stein; Shaohua Chang; Joseph A Hypolite; Yongmu Zheng; Stephen Zderic; Alan J Wein; Samuel Chacko Journal: Am J Physiol Cell Physiol Date: 2003-07-30 Impact factor: 4.249
Authors: Gerald M Herrera; Maria J Pozo; Peter Zvara; Georgi V Petkov; Chris T Bond; John P Adelman; Mark T Nelson Journal: J Physiol Date: 2003-06-17 Impact factor: 5.182