Urodynamic effects of intravesical administration of the new small/intermediate conductance calcium activated potassium channel activator NS309 in freely moving, conscious rats.
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.
Pandita
Raj Kumar
RK
Department of Clinical and Experimental Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden.
Rønn
Lars Christian B
LC
Jensen
Bo Skaaning
BS
Andersson
Karl-Erik
KE
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*
C493327:6,7-dichloro-1H-indole-2,3-dione 3-oxime; D007211:Indoles; D010091:Oximes