Effect of niflumic acid on noradrenaline-induced contractions of the rat aorta

Authors


Departmento de Farmacologia, Centro Biomédico - IB, Universidade do Estado do Rio de Janeiro, Brasil

Abstract

  • 1The effects of niflumic acid, an inhibitor of calcium-activated chloride channels, were compared with the actions of the calcium channel antagonist nifedipine on noradrenaline-evoked contractions in isolated preparations of the rat aorta.
  • 2The cumulative concentration-effect curve to noradrenaline (NA) was depressed by both nifedipine and niflumic acid in a reversible and concentration-dependent manner. The degree of inhibition of the maximal contractile response to NA (1 μm) produced by 10 μm niflumic acid (38%) was similar to the effect of 1 μm nifedipine (39%).
  • 3Contractions to brief applications (30 s) of 1 μm NA were inhibited by 55% and 62% respectively by 10 μm niflumic acid and 1 μm nifedipine.
  • 4In the presence of 0.1 μm nifedipine, niflumic acid (10 μm) produced no further inhibition of the NA-evoked contractions. Thus, the actions of niflumic acid and nifedipine were not additive.
  • 5In Ca-free conditions the transient contraction induced by 1 μm NA was not inhibited by niflumic acid (10 μm) and therefore this agent does not reduce the amount of calcium released from the intracellular store or reduce the sensitivity of the contractile apparatus to calcium.
  • 6Niflumic acid 10 μm did not inhibit the contractions produced by KCl (up to 120 mM) which were totally blocked by nifedipine. Contractions induced by 25 mM KCl were completely inhibited by 1 μm levcromakalim but were unaffected by niflumic acid.
  • 7It was concluded that niflumic acid produces selective inhibition of a component of NA-evoked contraction which is probably mediated by voltage-gated calcium channels. These data are consistent with a model in which NA stimulates a calcium-activated chloride conductance which leads to the opening of voltage-gated calcium channels to produce contraction.

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