DIFFERENCES IN THE CONTRACTILITY OF HUMAN ISOLATED PROSTATIC URETHRA TO OXYTOCIN AND NOREPINEPHRINE IN BENIGN PROSTATIC HYPERPLASIA: POTENTIAL ROLE OF OXYTOCIN IN BPH.

INTRODUCTION AND OBJECTIVES: Previously we have demonstrated that oxytocin (OT) can cause contraction of human prostate through oxytocin receptors. The aim of the present study was to evaluate whether OT can also produce contraction of human isolated prostatic urethra and determine whether this response is mediated by specific OT receptors using the selective oxytocin receptor antagonist epelsiban. METHODS: Prostatic urethra was obtained from 8 patients (67 3 years old) undergoing cystoprostatectomy for bladder cancer or prostatic adenomectomy for BPH. Strips were mounted under 1 g of initial tension. After a 60 min equilibration, strips were exposed to 30 mM norepinephrine (NE) to determine tissue viability. After wash-out and 60 min of re-equilibration, epelsiban (30, 100 and 300 nM) or its solvent (distilled water) were incubated for 60 min. Then, a single concentration of oxytocin (1 mM) was tested. In different strips, tamsulosin (10 nM) or its solvent (distilled water) were incubated for 45 min before each addition of NE (0.1-0.3-1-10-30 mM), added in a non cumulative manner RESULTS: In preliminary experiments it was determined that cumulative concentration response curves to OT and NE were not possible due to desensitization. In subsequent experiments, the magnitude of contractions induced by 1 mM oxytocin were 11.68 2.68% and 27.21 7.02% (of contractions to 30 mM NE) for strips from cancer and BPH patients respectively (p 1⁄4 0.0537). Epelsiban inhibited contractions induced by 1 mMOT. However due to the large variability in the response to OT (particularly between the two patient groups), coupled with the low n number (n1⁄45), effects did not reach statistical significance. NE (0.1 e 30 mM) added non-cumulatively, induced concentrationdependent contractions of human isolated prostatic urethra. Interestingly the magnitude of contractions induced by 30 mM NE were different between the two patient groups, however it was the reverse profile in comparison to OT (1.77 0.18 g and 0.99 0.16 g from bladder cancer and BPH patients respectively, p<0.01). Tamsulosin (10 nM) abolished the contractile effect of NE. CONCLUSIONS: This is the first demonstration of a contractile effect of OT in human prostatic urethra through specific OT receptors. In addition, OT appears to produce larger responses in tissue from BPH patients.