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.

Published

Journal Article

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 microM 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.

Full Text

Duke Authors

Cited Authors

  • Yu, Y; Fraser, MO; de Groat, WC

Published Date

  • January 16, 2004

Published In

Volume / Issue

  • 996 / 1

Start / End Page

  • 41 - 46

PubMed ID

  • 14670629

Pubmed Central ID

  • 14670629

International Standard Serial Number (ISSN)

  • 0006-8993

Digital Object Identifier (DOI)

  • 10.1016/j.brainres.2003.10.007

Language

  • eng

Conference Location

  • Netherlands