Effects of ZD6169, a K ATP channel opener, on neurally-mediated plasma extravasation in the rat urinary bladder induced by chemical or electrical stimulation of nerves

Abstract

The effects of oral administration of ZD6169, a potassium channel opener, on neurally mediated plasma extravasation in the urinary bladder and urethra were examined in urethane-anesthetized rats. Plasma extravasation was evaluated by measuring the tissue concentration of Evans blue, administered intravenously (50 mg/kg) 15 min prior to removal of tissues. Plasma extravasation was induced by three different stimuli: intravesical administration of either 0.25% acetic acid or 100 μM capsaicin or electrical stimulation of the pelvic nerve on one side (50 V, 10 s trains, 30 Hz intra-train frequency at 1 min intervals for 40 min). ZD6169 (5 mg/kg), administered orally 5 h prior to stimulation, significantly reduced the capsaicin-induced (50% decrease, p<0.05) or the electrical stimulation-induced (58% decrease, p<0.05) plasma extravasation in the bladder, but did not prevent the plasma extravasation in the bladder or urethra induced by intravesical infusion of 0.25% acetic acid. Administration of a K ATP channel blocker, glibenclamide (20 mg/kg, iv) 45 min prior to ZD6169 administration blocked the effects of ZD6169 on the electrical stimulation-induced plasma extravasation in the bladder and reduced the effects of ZD6169 on capsaicin-induced plasma extravasation. These findings indicate that ZD6169 (and/or a metabolite) can reduce neurogenic plasma extravasation in the bladder and are consistent with other studies indicating that ZD6169 can activate K ATP channels in C-fiber bladder afferents and suppress afferent activity.