title: Autonomous contractile activity in the isolated rat bladder is modulated by a TRPV1 dependent mechanism.
abstract: OBJECTIVE
  Resiniferatoxin (RTX), a vanilloid compound and agonist of the transient receptor potential channel 1 (TRPV1), is known for its beneficial effects on neurogenic detrusor overactivity. The mainstream rationale for its use is the desensitization of TRPV1 on sensory bladder afferents. However, recent findings showed that TRPV1 is present in other cell types in the bladder. To eliminate the effects of RTX on spinal and central neural circuits, we investigated autonomous contractility in normal and neurogenic rat bladders after treatment with RTX.
  
  
  METHODS
  Female Wistar rats were made paraplegic at vertebral level T8-T9. Animals were intravesically pre-treated with vehicle (ethanol 5%) or RTX (100 nM) and sacrificed after 72 hr. Each bladder was excised and placed in a heated organ bath, where intravesical pressures were measured. Effects on contractile parameters of intravesical volume load, the non-selective muscarinic receptor agonist carbachol (CA) and electrical stimulation (ES) of nerves were studied in both groups.
  
  
  RESULTS
  In RTX-treated normal bladders we found shorter contractions with higher amplitude than in control bladders (P < 0.05). In RTX-treated neurogenic bladders the amplitude and duration of autonomous contractions were increased compared with controls (P < 0.05). Furthermore RTX induced an increased response to CA and to ES (P < 0.05).
  
  
  CONCLUSIONS
  RTX significantly affected the properties of autonomous bladder contractile activity. This provides evidence for local effects of RTX on bladder contractile activity, which are not mediated by afferent neural pathways and which may contribute to the beneficial effects on detrusor overactivity. TRPV1 and TRPV1(+) cells seem to play an important role in (autonomous) bladder contractility.
authors.affiliation: Department of Urology, University Hospitals Gasthuisberg, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gevaert
authors.forename: Joachim
authors.initials: J
authors.lastname: Vandepitte
authors.forename: Dieter
authors.initials: D
authors.lastname: Ost
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ridder
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000819:agonists / Q000502:physiology*; D001743:Urinary Bladder / Q000294:innervation / Q000502:physiology*; D001750:Urinary Bladder, Neurogenic / Q000503:physiopathology*; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
chemical_list: D018679:Cholinergic Agonists; D004224:Diterpenes; D009498:Neurotoxins; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D002217:Carbachol; C024353:resiniferatoxin