EFFECT OF NIFLUMIC ACID ON NORADRENALINE-INDUCED CONTRACTIONS OF THE RAT AORTA

1 The effects of niflumic acid, an inhibitor of calcium-activated chlo ride channels, were compared with the actions of the calcium channel a ntagonist nifedipine on noradrenaline-evoked contractions in isolated preparations of the rat aorta. 2 The cumulative concentration-effect c urve to noradrenaline (NA) was depressed by both nifedipine and niflum ic acid in a reversible and concentration-dependent manner. The degree of inhibition of the maximal contractile response to NA (1 mu M) prod uced by 10 mu M niflumic acid (38%) was similar to the effect of 1 mu M nifedipine (39%). 3 Contractions to brief applications (30 s) of 1 m u M NA were inhibited by 55% and 62% respectively by 10 mu M niflumic acid and 1 mu M nifedipine. 4 In the presence of 0.1 mu M nifedipine, niflumic acid (10 mu M) produced no further inhibition of the NA-evoke d contractions. Thus, the actions of niflumic acid and nifedipine were not additive. 5 In Ca-free conditions the transient contraction induc ed by 1 mu M NA was not inhibited by niflumic acid (10 mu M) and there fore this agent does not reduce the amount of calcium released from th e intracellular store or reduce the sensitivity of the contractile app aratus to calcium. 6 Niflumic acid 10 mu M did not inhibit the contrac tions produced by KCl (up to 120 mM) which were totally blocked by nif edipine. Contractions induced by 25 mM KCl were completely inhibited b y 1 mu M levcromakalim but were unaffected by niflumic acid. 7 It was concluded that niflumic acid produces selective inhibition of a compon ent of NA-evoked contraction which is probably mediated by voltage-gat ed calcium channels. These data are consistent with a model in which N A stimulates a calcium-activated chloride conductance which leads to t he opening of voltage-gated calcium channels to produce contraction.