Abstract
Introduction and hypothesis
Effects of tadalafil, a phosphodiesterase type 5 inhibitor, on the urethral continence reflex induced by sneezing were investigated.
Methods
The amplitude of urethral pressure responses during sneezing (A-URS) and urethral baseline pressure (UBP) were measured in female rats using a microtransducer-tipped catheter. Sneeze leak-point pressure (S-LPP), defined as the lowest amount of pressure required to induce fluid leakage from the urethral orifice during sneezing, was measured in rats with stress urinary incontinence (SUI) induced by vaginal distension. Values were determined before and after tadalafil administration.
Results
Tadalafil dose dependently and significantly decreased A-URS and S-LPP. At the highest dose tested (6.0 mg/kg), A-URS and S-LPP decreased from 49.7 to 32.3 and from 63.9 to 44.2 cmH2O, respectively, whereas UBP did not significantly change.
Conclusions
Tadalafil attenuated the sneeze-induced urethral continence reflex by relaxing the striated muscles of the external urethral sphincter.
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References
Sairam K, Kulinskaya E, McNicholas TA, Boustead GB, Hanbury DC (2002) Sildenafil influences lower urinary tract symptoms. BJU Int 90(9):836–839
Yokoyama O, Yoshida M, Kim SC, Wang CJ, Imaoka T, Morisaki Y, Viktrup L (2013) Tadalafil once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a randomized placebo- and tamsulosin-controlled 12-week study in Asian men. Int J Urol 20(2):193–201
Lin G, Huang YC, Wang G, Lue TF, Lin CS (2010) Prominent expression of phosphodiesterase 5 in striated muscle of the rat urethra and levator ani. J Urol 184(2):769–774
DeLancey JO (1994) Structural support of the urethra as it relates to stress urinary incontinence: the hammock hypothesis. Am J Obstet Gynecol 170(6):1713–1720, discussion 1720–1713
Heesakkers JP, Gerretsen RR (2004) Urinary incontinence: sphincter functioning from a urological perspective. Digestion 69(2):93–101
Kamo I, Kaiho Y, Miyazato M, Torimoto K, Yoshimura N (2009) Two kinds of urinary continence reflexes during abrupt elevation of intravesical pressure in rats. Low Urin Tract Symptoms 1(s1):S40–S43
Kamo I, Torimoto K, Chancellor MB, de Groat WC, Yoshimura N (2003) Urethral closure mechanisms under sneeze-induced stress condition in rats: a new animal model for evaluation of stress urinary incontinence. Am J Physiol Regul Integr Comp Physiol 285(2):R356–R365
Kaiho Y, Kamo I, Chancellor MB, Arai Y, de Groat WC, Yoshimura N (2007) Role of noradrenergic pathways in sneeze-induced urethral continence reflex in rats. Am J Physiol Renal Physiol 292(2):F639–F646
Miyazato M, Kaiho Y, Kamo I, Chancellor MB, Sugaya K, de Groat WC, Yoshimura N (2008) Effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, on sneeze-induced urethral continence reflex in rats. Am J Physiol Renal Physiol 295(1):F264–F271
Lin AS, Carrier S, Morgan DM, Lue TF (1998) Effect of simulated birth trauma on the urinary continence mechanism in the rat. Urology 52(1):143–151
Damaser MS, Broxton-King C, Ferguson C, Kim FJ, Kerns JM (2003) Functional and neuroanatomical effects of vaginal distention and pudendal nerve crush in the female rat. J Urol 170(3):1027–1031
Anderson RS, Shepherd AM, Feneley RC (1983) Microtransducer urethral profile methodology: variations caused by transducer orientation. J Urol 130(4):727–728
Tinel H, Stelte-Ludwig B, Hutter J, Sandner P (2006) Pre-clinical evidence for the use of phosphodiesterase-5 inhibitors for treating benign prostatic hyperplasia and lower urinary tract symptoms. BJU Int 98(6):1259–1263
Fibbi B, Morelli A, Vignozzi L, Filippi S, Chavalmane A, De Vita G, Marini M, Gacci M, Vannelli GB, Sandner P, Maggi M (2010) Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med 7(1 Pt 1):59–69
Ho KM, McMurray G, Brading AF, Noble JG, Ny L, Andersson KE (1998) Nitric oxide synthase in the heterogeneous population of intramural striated muscle fibres of the human membranous urethral sphincter. J Urol 159(3):1091–1096
Hampel C, Wienhold D, Benken N, Eggersmann C, Thuroff JW (1997) Definition of overactive bladder and epidemiology of urinary incontinence. Urology 50(6A Suppl):4–14, discussion 15–17
Herr HW (1994) Quality of life of incontinent men after radical prostatectomy. J Urol 151(3):652–654
Kaiho Y, Yamashita S, Arai Y (2013) Optimization of sexual function outcome after radical prostatectomy using phosphodiesterase type 5 inhibitors. Int J Urol 20(3):285–289
Gacci M, Ierardi A, Rose AD, Tazzioli S, Scapaticci E, Filippi S, Maggi M, Nicita G, Carini M, Montorsi F (2010) Vardenafil can improve continence recovery after bilateral nerve sparing prostatectomy: results of a randomized, double blind, placebo-controlled pilot study. J Sex Med 7(1 Pt 1):234–243
Acknowledgments
This work was supported by Japan Society for the Promotion of Science KAKENHI Grant Number 23650317.
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Izumi, H., Kaiho, Y., Miyazato, M. et al. Effects of phosphodiesterase type 5 inhibitor, tadalafil, on continence reflex in rats. Int Urogynecol J 25, 1721–1727 (2014). https://doi.org/10.1007/s00192-014-2453-3
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DOI: https://doi.org/10.1007/s00192-014-2453-3