title: Tadalafil enhances the inhibitory effects of tamsulosin on neurogenic contractions of human prostate and bladder neck.
abstract: BACKGROUND
  Lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTSs) may be associated with erectile dysfunction (ED). Phosphodiesterase type 5 (PDE5) inhibitors used for treating ED have shown clinical benefit in patients with LUTS but their actions in human LUT tissues are not well defined.
  
  
  OBJECTIVE
  To determine the effects of the long-acting PDE5 inhibitor, tadalafil, on smooth muscle tone in human prostate and bladder neck as well as to evaluate the influence of tadalafil on the efficacy of the α-adrenergic receptor antagonist, tamsulosin, in inhibiting contractile responses in these tissues.
  
  
  METHODS
  Strips of human peripheral prostate (HPP), human internal prostate (HIP), and human bladder neck (HBN) were obtained from organ donors and patients with BPH. The strips were then disposed in organ baths to evaluate nitric oxide/cyclic guanosine monophosphate (cGMP)-mediated relaxation and cGMP kinetics in HPP and HIP, and electrical field stimulation (EFS)-induced neurogenic contractions in HPP and HBN.
  
  
  METHODS
  Tadalafil-induced effects on sodium nitroprusside (SNP)-induced relaxation and cGMP accumulation in HPP and HIP and influence of tadalafil and tamsulosin on EFS-induced contractions of HPP and HBN.
  
  
  RESULTS
  SNP-induced relaxation of HPP and HIP was significantly potentiated by tadalafil (30-60 nM). SNP-induced cGMP accumulation in HPP and HIP was enhanced by tadalafil (30-60 nM), but significant difference was only obtained in HPP. EFS-induced contractions sensitive to tetrodotoxin in HPP were significantly inhibited by tadalafil (30 nM) but not by tamsulosin (0.01-100 nM) or vehicle. Further inhibition of neurogenic responses in HPP was achieved by combining tadalafil and tamsulosin treatments. Tamsulosin, but not tadalafil, significantly reduced EFS-induced contractions in HBN, but the coadministration of both therapies resulted in additional inhibition of contractions.
  
  
  CONCLUSIONS
  While tadalafil enhances cGMP accumulation and potentiates prostate relaxation, tadalafil combined with tamsulosin results in enhanced inhibition of neurogenic contractions of HPP and HBN.
authors: Servicio de Histología, Departamento de Investigación, Hospital Universitario Ramón y Cajal, Madrid, Spain. javier.angulo@hrc.es
authors: Javier
authors: J
authors: Angulo
authors: Pedro
authors: P
authors: Cuevas
authors: Argentina
authors: A
authors: Fernández
authors: José M
authors: JM
authors: La Fuente
authors: Antonio
authors: A
authors: Allona
authors: Ignacio
authors: I
authors: Moncada
authors: Iñigo
authors: I
authors: Sáenz de Tejada
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology*; D004558:Electric Stimulation; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D011467:Prostate / Q000503:physiopathology*; D011470:Prostatic Hyperplasia / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology; D000068581:Tadalafil; D000077409:Tamsulosin; D001743:Urinary Bladder / Q000503:physiopathology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D002243:Carbolines; D020030:Nitric Oxide Donors; D058986:Phosphodiesterase 5 Inhibitors; D013449:Sulfonamides; D009599:Nitroprusside; D000068581:Tadalafil; D000077409:Tamsulosin