Low concentrations of niflumic acid enhance basal spontaneous and carbachol-induced contractions of the detrusor

Int Urol Nephrol. 2014 Feb;46(2):349-57. doi: 10.1007/s11255-013-0550-8. Epub 2013 Sep 15.

Abstract

Purpose: The urinary bladder expresses Ca(2+)-activated Cl(-) channels (CACC), but its physiological role in governing contractility remains to be defined. The CACC modulator niflumic acid (NFA) is widely used despite the variable results arisen from different drug concentrations used. This study was designed to examine the effects of NFA at low concentrations on detrusor strip contractility.

Methods: Rat detrusor strips with mucosa-intact (+MU) and mucosa-denuded (-MU) were prepared in transverse (Tr) and longitudinal (Lg) with respect to the bladder orientation. Isometric force measurements were made at baseline (for spontaneous phasic contractile activity) and during drug stimulation (by carbachol, CCh) with and without NFA.

Results: NFA (1 and 10 μmol/L) pretreatment enhanced CCh-induced contractions more in +MU than -MU strips with no selectivity on contractile direction. For spontaneous phasic contractions, NFA-treated strips in the Tr direction showed increased phasic amplitude, while phasic frequency was unchanged.

Conclusions: The findings suggest low concentrations of NFA having a potentiating effect on detrusor contractions that was sensitive to the MU and contractile direction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbachol / pharmacology
  • Cholinergic Agonists / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Isometric Contraction / drug effects*
  • Male
  • Mucous Membrane / physiology*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Niflumic Acid / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Urinary Bladder / drug effects*
  • Urinary Bladder / physiology

Substances

  • Cholinergic Agonists
  • Cyclooxygenase Inhibitors
  • Niflumic Acid
  • Carbachol