Urodynamic effects of intravesical administration of the new small/intermediate conductance calcium activated potassium channel activator NS309 in freely moving, conscious rats.

Abstract

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. 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. 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. 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.