437 CONTRACTION/RELAXATION RESPONSE STUDIES ON HUMAN MALE URETHRAL SMOOTH MUSCLE: AN IN VITRO APPROACH (2010)

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology II1 Apr 2010437 CONTRACTION/RELAXATION RESPONSE STUDIES ON HUMAN MALE URETHRAL SMOOTH MUSCLE: AN IN VITRO APPROACH George Kedia, Stefan Ückert, Michael Seidler, Joachim Sonnenberg, and Markus Kuczyk George KediaGeorge Kedia More articles by this author , Stefan ÜckertStefan Ückert More articles by this author , Michael SeidlerMichael Seidler More articles by this author , Joachim SonnenbergJoachim Sonnenberg More articles by this author , and Markus KuczykMarkus Kuczyk More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.508AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The smooth musculature of the male and female urethra is considered to contribute to the mechanism of urinary continence and the control of micturition. It has been supposed that endogenous compounds mediate the resistance of the bladder outlet and urethra during the filling phase while cyclic nucleotide-mediated pathways produce relaxation during emptying of the bladder. Up until now, only minimal research has been conducted in order to evaluate the responses of isolated human urethra to compounds known to affect smooth muscle tension. The present study aimed to elucidate the functional responses of isolated human urethral smooth muscle to various contractile and relaxant agents. METHODS Specimens of human penile urethra were obtained from 16 male subjects (mean age: 47 y) who had undergone male-to-female gender reassignment surgery. Using the organ bath technique, the contraction of urethral smooth muscle induced by increasing concentrations (1 nM - 10 μM) of norepinephrine (NE), phenylephrine (PE), carbachol (Carb), prostaglandin F2 alpha (PGF2 alpha), endothelin-1 (ET-1), angiotensin II (Ang-II), and oxytocin (OT) was measured. In another set-up, the tissue was contracted by NE (10 μM). After a stable tension had been reached, the C-type natriuretic peptide (CNP) (0.1 nM - 1 μM), nitric oxide donor drug sodium nitroprusside (SNP), adenylyl cyclase activator forskolin, alpha-antagonist delquamine, acetylcholine, and phosphodiesterase 5 (PDE5) inhibitor sildenafil (1nM - 10 μM) were added in a cumulative manner and isometric responses recorded. RESULTS Urethral smooth muscle was dose-dependently contracted by ET-1 (158% of the force generated by 80 mM KCl), OT (80% of KCl), NE (60.6% of KCl), PGF2 alpha (57.3% of KCl), and PE (40.8% of KCl) whereas no or only very minor effects of carbachol or Ang-II were registered. The contraction induced by NE was effectively reversed by SNP (-68±19% reversion of tension), delquamine (-57±16%), and CNP (-30±11%, at 1 μM), In contrast, the relaxation produced by sildenafil (-35±18%), forskolin (-27±18%) and acetylcholine (-22±8%) was less pronounced. CONCLUSIONS Physiological concentrations of ET-1, OT, NE and PGF2 alpha induced contraction of urethral smooth muscle while relaxant actions of SNP, CNP, sildenafil and forskolin were registered. These findings might be of importance with regard to the identification of new pharmacological avenues to facilitate the contraction and relaxation of the outflow region. Hannover, Germany© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183 Issue 4S April 2010 Page: e173 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.Metrics Author Information George Kedia More articles by this author Stefan Ückert More articles by this author Michael Seidler More articles by this author Joachim Sonnenberg More articles by this author Markus Kuczyk More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...