title: Inhibitory effects of phosphodiesterase 5 inhibitor, tadalafil, on mechanosensitive bladder afferent nerve activities of the rat, and on acrolein-induced hyperactivity of these nerves.
abstract: What's known on the subject? and What does the study add? Tadalafil, a phosphodiesterase type 5 inhibitor, might be effective for not only erectile dysfunction but also lower urinary tract symptoms (LUTS). One of the mechanisms of tadalafil on LUTS is added in the study.
  
  
  OBJECTIVE
  To determine if tadalafil, a phosphodiesterase type 5 inhibitor, decreases afferent nerve activity from the bladder with and without chemical stimulation by intravesical acrolein instillation.
  
  
  METHODS
  Female Sprague-Dawley rats were used. Under urethane anaesthesia, single afferent fibres of the nerve primarily originating from the bladder were identified by electrical stimulation of the pelvic nerve and by bladder distension, and classified by conduction velocity as Aδ- or C-fibres. After measuring the baseline single afferent activities (SAA) during constant filling, two experiments were performed. First, tadalafil was administrated intravenously (i.v.) at three doses, 0.01, 0.03 and 0.1 mg/kg cumulatively and SAA were repeatedly studied after each administration. Second, in the presence of vehicle or tadalafil (0.1 mg/kg) i.v., the effect of intravesical instillation of acrolein (0.003%) was studied.
  
  
  RESULTS
  In all, 39 single units were isolated (Aδ-fibres 21; C-fibres, 18) in 25 rats. Tadalafil dose-dependently decreased SAA of both Aδ- and C-fibres during saline instillation. Intravesical acrolein facilitated SAA of both fibres after vehicle administration. Pretreatment with tadalafil significantly inhibited the acrolein-induced hyperactivity of both fibres.
  
  
  CONCLUSIONS
  Our study shows, using selective unifibre potential measurement, that systemic administration of tadalafil reduces mechanosensitive afferent activities of both Aδ- and C-fibres elicited by bladder distension in the rat, and also that tadalafil has an inhibitory effect on the increased activities of both fibres induced by intravesical acrolein instillation.
authors.affiliation: Department of Urology, Antwerp University Hospital and Antwerp University, Faculty of Medicine, Antwerp, Belgium.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Minagawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Aizawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Wyndaele
mesh_terms: D000171:Acrolein / Q000494:pharmacology; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D005260:Female; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068581:Tadalafil; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*
chemical_list: D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil; D000171:Acrolein