PURPOSE: 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. MATERIALS AND 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.
PURPOSE: 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. MATERIALS AND 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: Shankar P Parajuli; Kiril L Hristov; Rupal P Soder; Whitney F Kellett; Georgi V Petkov Journal: Br J Pharmacol Date: 2013-04 Impact factor: 8.739
Authors: K S Thorneloe; A M Knorn; P E Doetsch; E S R Lashinger; A X Liu; C T Bond; J P Adelman; M T Nelson Journal: Am J Physiol Regul Integr Comp Physiol Date: 2008-03-19 Impact factor: 3.619