title: Relaxant effects of sildenafil on the human isolated bladder neck.
abstract: OBJECTIVE
  To evaluate potential in vitro relaxant actions of sildenafil on human isolated bladder neck smooth muscle.
  
  
  METHODS
  Bladder neck strips were sampled from patients (aged 55-77 years) submitted to prostatic surgery (6 adenomectomies and 1 radical prostatectomy). These were carefully dissected into 1-2 x 0.5-cm pieces and suspended in an organ bath containing 30 mL of a modified Krebs Henseleit solution, bubbled with 95% O(2)/5% CO(2). After tissue stabilization and viability test with KCl, the tissue was precontracted with phenylephrine, and a concentration-response relaxant curve to sildenafil was constructed. The effect of sildenafil was also assessed in tissues treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (inhibitors of nitric oxide synthase and guanylyl cyclase, respectively).
  
  
  RESULTS
  Sildenafil induced significant bladder neck relaxation at all concentrations tested. The maximum relaxation was 86.97% +/- 6.69%, obtained with a high concentration of sildenafil (5.1 x 10(-4) M). Both L-NAME and ODQ significantly reduced sildenafil-induced relaxation.
  
  
  CONCLUSIONS
  Sildenafil was effective in inducing bladder neck smooth muscle relaxation in vitro. This effect was almost abolished by L-NAME and ODQ, clearly demonstrating a dependence of the nitric oxide-cyclic guanosine monophosphate pathway. Our in-vitro results suggest that sildenafil might be useful in improving lower urinary tract symptoms due to benign prostatic hyperplasia.
authors.affiliation: Urology Service, State University of Rio de Janeiro, Rio de Janeiro, Brazil. drbittencourt@yahoo.com.br
authors.forename: José Augusto F
authors.initials: JA
authors.lastname: Bittencourt
authors.forename: Tania
authors.initials: T
authors.lastname: Tano
authors.forename: Sessin A
authors.initials: SA
authors.lastname: Gajar
authors.forename: Angela C
authors.initials: AC
authors.lastname: Resende
authors.forename: Miguel
authors.initials: M
authors.lastname: de Lemos Neto
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Damião
authors.forename: David N
authors.initials: DN
authors.lastname: Criddle
authors.forename: Graziele Freitas
authors.initials: GF
authors.lastname: de Bem
authors.forename: Roberto Soares
authors.initials: RS
authors.lastname: de Moura
mesh_terms: D000368:Aged; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology*
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate