Login to Access Video or Poster Abstract: MP94-09
Sources of Funding: NIH R01DK107450

Introduction

The spinal serotonergic pathways are reportedly involved in the control of urethral continence reflexes that prevent stress urinary incontinence (SUI). We previously demonstrated that serotonin (5HT) receptor subtypes, 5HT_1A and 5HT_2C, respectively reduce and enhance the urethral continence reflex during sneezing in rats. However, because there are other multiple excitatory and inhibitory 5HT receptors, the overall effects of the 5HT system on the urethral function are not well elucidated. Therefore, in this study, we examined the effects of 5HT depletion induced by p-chlorophenylalanine (PCPA) that inhibits 5HT synthesis, on urethral baseline activity and reflex contractions during sneezing in rats.

Methods

We used female 12-week-aged Sprague-Dawley rats, which were divided into two groups; vehicle-administered (Normal, n = 6) and PCPA-administered groups (PCPA, n = 5). PCPA (200 mg/kg/day) was administered intraperitoneally for two days. Thereafter, using a microtransducer-tipped catheter inserted to the mid-urethra, we assessed urethral baseline pressure (UBP) and the amplitude of urethral responses during sneezing (AURS) under urethane anesthesia. UBP was determined from a plateau section of pressure recordings just before inducing sneezing, which was induced by intranasal stimulation with a whisker. AURS values were measured as the urethral maximal pressure change from baseline during sneezing. To evaluate induced sneeze intensity, abdominal pressure during sneezing (Pabd) was also measured via an intraabdominal balloon catheter. All data are shown in cmH₂O.

Results

UBP and AURS were both significantly decreased in the PCPA group (17.8 and 36.7) compared to the Normal group (31.1 and 71.8), respectively (Figure). There was no statistical difference in Pabd between two groups (Normal; 18.2, PCPA; 28.3).

Conclusions

This result indicates that activation of the serotonergic system contributes to maintaining the urethral baseline activity and the urethral continence reflex during stress conditions such as sneezing, which are reportedly attributable to contractions of smooth and striated urethral sphincter muscles, respectively. Also, 5HT-depleted rats could be a suitable SUI model to investigate the effects of 5HT receptor subtype-selective agonists on urethral continence function._x000D_

Funding

NIH R01DK107450