Impaired contractility of the circular striated urethral sphincter muscle may contribute to stress urinary incontinence in female zucker fatty rats

Abstract

AIM Obesity has been an independent risk factor for female stress urinary incontinence (SUI), the mechanism of this association remains unknown. The aim of this study is to validate the hypothesis that urethral dysfunction is a possible contributor to SUI in obese women. METHODS Ten Zucker Fatty (ZF) (ZUC-Leprfa 185) and 10 Zucker Lean (ZL) (ZUC-Leprfa 186) female rats at 12-week-old were used in this experiment. The urethral sphincter rings were harvested from the bladder neck through to the most proximal 2/3 regions. In the organ bath study, single pulses of electrical field stimulation (EFS) were applied. For the fatiguing stimulation, repeated multi-pulse EFS with 70 mA were applied at frequency of 5 Hz for 5 min. Caffeine-containing Krebs’ solution was administrated to contract the urethra until the contraction began to reach a plateau for 10 min. We performed immunofluorescence staining of the urethra after the experiment was finished. RESULTS Compared to ZL controls, ZF rats had significantly impaired muscle contractile activity (MCA) (P < 0.05). Also, ZF rats presented early fatiguing of MCA and had a significantly greater percentage of MCA decline from baseline in the fatiguing test (37.7% vs 25.6%, P < 0.05). The plateau of maximal MCA induced by caffeine in ZF rats was significantly lower than ZL controls (0.22 vs 0.36, P < 0.05). CONCLUSIONS This novel study showed that obese female rats had significantly impaired contractile properties of striated urethral sphincter, suggesting urethral dysfunction could be an important contributor to SUI in obesity.

The effects of microenergy acoustic pulses on animal model of obesity‐associated stress urinary incontinence. Part 2: In situ activation of pelvic floor and urethral striated muscle progenitor cells

“…However, exact mechanisms of obesity‐associated stress urinary incontinence (OA‐SUI) are not clear. Our previous study demonstrated that obesity can lead to intra‐myocellular lipid deposition in the urethral sphincter and to atrophy and distortion of urethral striated muscle …”

“…Our recent study indicates that obesity actually impairs the contractile properties of the urethral sphincter through intramyocellular lipid deposition, which leads to atrophy and distortion of the urethral striated muscle, an important contributor to obesityassociated-SUI (OA-SUI). 1,2 Current options for treatment of OA-SUI include oral medications, urethral bulking agents, and urethral sling surgeries, however, limited efficacy or short-term and long-term complications may occur. 3,4 Recently, exogenous stem cells have been applied to treat SUI-associated neuronal and muscular deficiencies, [5][6][7][8] but bear some negative side effects.…”

The effects of microenergy acoustic pulses on an animal model of obesity‐associated stress urinary incontinence. Part 1: Functional and histologic studies

“…In our previous work, Lin Wang et al established the ZUC‐Lepr fa 185 female fatty rat as a consistent and reliable animal model to study OA‐SUI. Lee et al used young 12‐week‐old rats and conducted ex vivo tissue bath studies to check the contractile activity of urethral sphincters. Our results show that the striated muscle length in ZF rats is shorter than in ZL rats.…”

“…Conscious cystometry was measured as previously described . For LPP measurement, under proper anesthesia, rats were placed in a supine position and an incision was made to expose the bladder.…”

“…In our previous studies, we demonstrated the histologic changes of the urethral sphincter striated muscle in obese rats as compared to lean rats. Gasbarro et al used female rats to study the effects of obesity on the lower urinary tract by evaluating voiding function and urethral anatomy.…”