Kv 7 Positive Modulators Reduce Detrusor Overactivity and Increase Bladder Capacity in Rats

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Kv 7 Positive Modulators Reduce Detrusor Overactivity and Increase Bladder Capacity in Rats. / Svalø, Julie; Hansen, Henrik H; Rønn, Lars Christian B; Sheykhzade, Majid; Munro, Gordon; Rode, Frederik; Jakobsen, Julie Svalø.

In: Basic & Clinical Pharmacology & Toxicology Online, Vol. 110, No. 2, 02.2012, p. 145-153.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Svalø, J, Hansen, HH, Rønn, LCB, Sheykhzade, M, Munro, G, Rode, F & Jakobsen, JS 2012, 'Kv 7 Positive Modulators Reduce Detrusor Overactivity and Increase Bladder Capacity in Rats', Basic & Clinical Pharmacology & Toxicology Online, vol. 110, no. 2, pp. 145-153. https://doi.org/10.1111/j.1742-7843.2011.00765.x

APA

Svalø, J., Hansen, H. H., Rønn, L. C. B., Sheykhzade, M., Munro, G., Rode, F., & Jakobsen, J. S. (2012). Kv 7 Positive Modulators Reduce Detrusor Overactivity and Increase Bladder Capacity in Rats. Basic & Clinical Pharmacology & Toxicology Online, 110(2), 145-153. https://doi.org/10.1111/j.1742-7843.2011.00765.x

Vancouver

Svalø J, Hansen HH, Rønn LCB, Sheykhzade M, Munro G, Rode F et al. Kv 7 Positive Modulators Reduce Detrusor Overactivity and Increase Bladder Capacity in Rats. Basic & Clinical Pharmacology & Toxicology Online. 2012 Feb;110(2):145-153. https://doi.org/10.1111/j.1742-7843.2011.00765.x

Author

Svalø, Julie ; Hansen, Henrik H ; Rønn, Lars Christian B ; Sheykhzade, Majid ; Munro, Gordon ; Rode, Frederik ; Jakobsen, Julie Svalø. / Kv 7 Positive Modulators Reduce Detrusor Overactivity and Increase Bladder Capacity in Rats. In: Basic & Clinical Pharmacology & Toxicology Online. 2012 ; Vol. 110, No. 2. pp. 145-153.

Bibtex

@article{b3b18254bbce4865bef06527dbd9e4c8,
title = "Kv 7 Positive Modulators Reduce Detrusor Overactivity and Increase Bladder Capacity in Rats",
abstract = "  The effects of the Kv 7 channel modulators retigabine (opener) and XE991 (blocker) on rat bladder function were investigated ex vivo and in vivo to assess the potential of Kv 7 openers for the treatment of overactive bladder. In organ bath studies, capsaicin-stimulated rat urinary bladder rings were exposed to retigabine and XE991 and the effect on tension and amplitude was evaluated. In anaesthetized rats, retigabine (0.01-1 mg/kg, i.v.) effects on bladder function, in which overactivity was induced by continuous infusion of 0.5% acetic acid, were assessed. The effect of retigabine (10 mg/kg, p.o.) on cystometric parameters was also measured in conscious rats with capsaicin-induced irritated bladders. Localization of Kv 7 subunits within bladder tissue was analysed by RT-qPCR and western blotting. In organ bath studies, retigabine robustly reduced capsaicin-induced contractility of bladder rings and this effect was blocked by XE991 confirming the specificity of action via Kv 7 channels. In anaesthetized rats with acetic acid-irritated bladders, retigabine markedly increased bladder capacity with no concomitant reduction in blood pressure. Retigabine also reduced bladder pressure and delayed voiding in conscious rats with capsaicin-irritated bladders. Kv 7.1, Kv 7.4 and Kv 7.5 subunit mRNA transcripts were detected in rat bladder. Western blot analysis confirmed that Kv 7.4 subunit protein was expressed in rat bladder. These results suggest that retigabine and other Kv 7 channel positive modulators may have beneficial effects on bladder overactivity partly via activation of Kv 7 channels expressed in bladder tissue.",
author = "Julie Sval{\o} and Hansen, {Henrik H} and R{\o}nn, {Lars Christian B} and Majid Sheykhzade and Gordon Munro and Frederik Rode and Jakobsen, {Julie Sval{\o}}",
note = "{\textcopyright} 2011 The Authors. Basic & Clinical Pharmacology & Toxicology {\textcopyright} 2011 Nordic Pharmacological Society.",
year = "2012",
month = feb,
doi = "10.1111/j.1742-7843.2011.00765.x",
language = "English",
volume = "110",
pages = "145--153",
journal = "Basic and Clinical Pharmacology and Toxicology",
issn = "1742-7835",
publisher = "Wiley-Blackwell",
number = "2",

}

RIS

TY - JOUR

T1 - Kv 7 Positive Modulators Reduce Detrusor Overactivity and Increase Bladder Capacity in Rats

AU - Svalø, Julie

AU - Hansen, Henrik H

AU - Rønn, Lars Christian B

AU - Sheykhzade, Majid

AU - Munro, Gordon

AU - Rode, Frederik

AU - Jakobsen, Julie Svalø

N1 - © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

PY - 2012/2

Y1 - 2012/2

N2 -   The effects of the Kv 7 channel modulators retigabine (opener) and XE991 (blocker) on rat bladder function were investigated ex vivo and in vivo to assess the potential of Kv 7 openers for the treatment of overactive bladder. In organ bath studies, capsaicin-stimulated rat urinary bladder rings were exposed to retigabine and XE991 and the effect on tension and amplitude was evaluated. In anaesthetized rats, retigabine (0.01-1 mg/kg, i.v.) effects on bladder function, in which overactivity was induced by continuous infusion of 0.5% acetic acid, were assessed. The effect of retigabine (10 mg/kg, p.o.) on cystometric parameters was also measured in conscious rats with capsaicin-induced irritated bladders. Localization of Kv 7 subunits within bladder tissue was analysed by RT-qPCR and western blotting. In organ bath studies, retigabine robustly reduced capsaicin-induced contractility of bladder rings and this effect was blocked by XE991 confirming the specificity of action via Kv 7 channels. In anaesthetized rats with acetic acid-irritated bladders, retigabine markedly increased bladder capacity with no concomitant reduction in blood pressure. Retigabine also reduced bladder pressure and delayed voiding in conscious rats with capsaicin-irritated bladders. Kv 7.1, Kv 7.4 and Kv 7.5 subunit mRNA transcripts were detected in rat bladder. Western blot analysis confirmed that Kv 7.4 subunit protein was expressed in rat bladder. These results suggest that retigabine and other Kv 7 channel positive modulators may have beneficial effects on bladder overactivity partly via activation of Kv 7 channels expressed in bladder tissue.

AB -   The effects of the Kv 7 channel modulators retigabine (opener) and XE991 (blocker) on rat bladder function were investigated ex vivo and in vivo to assess the potential of Kv 7 openers for the treatment of overactive bladder. In organ bath studies, capsaicin-stimulated rat urinary bladder rings were exposed to retigabine and XE991 and the effect on tension and amplitude was evaluated. In anaesthetized rats, retigabine (0.01-1 mg/kg, i.v.) effects on bladder function, in which overactivity was induced by continuous infusion of 0.5% acetic acid, were assessed. The effect of retigabine (10 mg/kg, p.o.) on cystometric parameters was also measured in conscious rats with capsaicin-induced irritated bladders. Localization of Kv 7 subunits within bladder tissue was analysed by RT-qPCR and western blotting. In organ bath studies, retigabine robustly reduced capsaicin-induced contractility of bladder rings and this effect was blocked by XE991 confirming the specificity of action via Kv 7 channels. In anaesthetized rats with acetic acid-irritated bladders, retigabine markedly increased bladder capacity with no concomitant reduction in blood pressure. Retigabine also reduced bladder pressure and delayed voiding in conscious rats with capsaicin-irritated bladders. Kv 7.1, Kv 7.4 and Kv 7.5 subunit mRNA transcripts were detected in rat bladder. Western blot analysis confirmed that Kv 7.4 subunit protein was expressed in rat bladder. These results suggest that retigabine and other Kv 7 channel positive modulators may have beneficial effects on bladder overactivity partly via activation of Kv 7 channels expressed in bladder tissue.

U2 - 10.1111/j.1742-7843.2011.00765.x

DO - 10.1111/j.1742-7843.2011.00765.x

M3 - Journal article

C2 - 21895977

VL - 110

SP - 145

EP - 153

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

SN - 1742-7835

IS - 2

ER -

ID: 128887603