title: Mechanisms involved in testosterone-induced relaxation to the pig urinary bladder neck.
abstract: OBJECTIVE
  Testosterone replacement therapy improves bladder capacity in urinary tract dysfunction. There is no information, however, about the role of this steroid hormone on the muscle tension of the bladder outflow region. The current study investigated the mechanisms underlying the testosterone-induced action in the pig bladder neck.
  
  
  METHODS
  Urothelium-denuded bladder neck strips were mounted in myographs for isometric force recordings and for simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension. The relaxations to testosterone, the non-aromatizable metabolite 4,5α-dihydrotestosterone (DHT) and electrical field stimulation (EFS) were carried out on phenylephrine (PhE)-precontracted strips.
  
  
  RESULTS
  Testosterone and DHT evoked similar concentration-dependent relaxations only at very high pharmacological concentrations. The presence of the urothelium and the inhibition of intracellular androgenic receptor (AR), aromatase, 5α-reductase, nitric oxide (NO) synthase, guanylyl cyclase, cyclooxygenase (COX), large-, intermediate- and small-Ca(2+)-activated K(+) channels or ATP-dependent K(+) channels failed to modify the testosterone relaxations. Neuronal voltage-gated Ca(2+) (VOC) channels and voltage-gated K(+) (K(V)) channel blockers potentiated these responses. EFS evoked frequency-dependent relaxations, which were not changed by threshold concentrations of testosterone. In Ca(2+)-free potassium rich physiological saline solution, testosterone inhibited the contractions induced by CaCl(2) and the L-type VOC channel activator (±)-BAY K 8644. Relaxations elicited by testosterone were accompanied by simultaneous decreases in smooth muscle [Ca(2+)](i).
  
  
  CONCLUSIONS
  Testosterone produces relaxation of the pig urinary bladder neck through mechanisms independent of urothelium, AR, aromatase, 5α-reductase, NO synthase, guanylyl cyclase, COX and K(+) channels. Testosterone-induced relaxation is produced via the inhibition of the extracellular Ca(2+) entry through L-type VOC channels.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Vítor S
authors.initials: VS
authors.lastname: Fernandes
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Barahona
authors.forename: Paz
authors.initials: P
authors.lastname: Recio
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez-Sáenz
authors.forename: Ana S F
authors.initials: AS
authors.lastname: Ribeiro
authors.forename: Cristina
authors.initials: C
authors.lastname: Contreras
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Martínez
authors.forename: Salvador
authors.initials: S
authors.lastname: Bustamante
authors.forename: Joaquín
authors.initials: J
authors.lastname: Carballido
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
authors.forename: Medardo
authors.initials: M
authors.lastname: Hernández
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013552:Swine; D013739:Testosterone / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019459:Urothelium / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D014662:Vasoconstrictor Agents; D013196:Dihydrotestosterone; D010656:Phenylephrine; D013739:Testosterone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011188:Potassium; D002118:Calcium