title: Urodynamic effects of intravesical administration of the new small/intermediate conductance calcium activated potassium channel activator NS309 in freely moving, conscious rats.
abstract: OBJECTIVE
  We investigated the effects of the new K+ channel activator NS309, which acts on small and intermediate conductance Ca2+ activated K+ channels, on detrusor activity in normal rats.
  
  
  METHODS
  NS309 was given intravesically at different concentrations to conscious female Sprague-Dawley rats undergoing continuous cystometry. The effects of the drug on oxyhemoglobin induced detrusor overactivity were also tested.
  
  
  RESULTS
  Intravesical NS309 (100, 300 and 1,000 ng ml(-1)) increased bladder capacity, micturition volume and intercontraction intervals in a concentration dependent way. NS309 (1,000 ng ml(-1)) given intravesically for 1 hour before instillation of intravesical oxyhemoglobin (250 microM) decreased or completely prevented the detrusor overactivity induced by oxyhemoglobin.
  
  
  CONCLUSIONS
  Opening small and intermediate conductance Ca2+ activated K+ channels with NS309 given intravesically increased bladder capacity, micturition volume and intercontraction intervals in a concentration dependent way and prevented oxyhemoglobin induced detrusor overactivity. Results suggest that these channels can be interesting targets for drugs aiming to control micturition.
authors.affiliation: Department of Clinical and Experimental Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden.
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Pandita
authors.forename: Lars Christian B
authors.initials: LC
authors.lastname: Rønn
authors.forename: Bo Skaaning
authors.initials: BS
authors.lastname: Jensen
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D003243:Consciousness; D005260:Female; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D010091:Oximes / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology*; D014563:Urodynamics / Q000187:drug effects*
chemical_list: C493327:6,7-dichloro-1H-indole-2,3-dione 3-oxime; D007211:Indoles; D010091:Oximes