Pre- and Postsynaptic effects of tetrodotoxin flecainide and pilsicainide in the rabbit tracheal smooth muscle

The aim of this in vitro study was ta investigate the inhibitory and relaxant effects of sodium channel blockers, tetrodotoxin (TTX, 10-8 - 10-6 M), flecainide (10-6 - 3x10-4 M) and pilsicainide (10-6 - 3x104 M), on both electrical field stimulation (EFS)- and car-bachol-induced contractions in the rabbit trachea. In addition, the role of nitric oxide or cyclooxygenase products synthesized from epithelium in the pre- and postsynaptic effects of these agents was in-vestigated. EFS (20 sec at 40-50 V, 20 Hz, 1 msec) pro-duced reproducible contractions in the tracheal strips. Al! of the sodium channel blockers used in-hibited EFS-induced contraction in a concentration-dependent manner. The rank order of potency for in-hibition of EFS-induced response was TTX > fle-cainide > pilsicainide. TTX did not influence the car-bachol-induced contractions. Carbachol-induced contractions of tracheal strips were dose-dependently inhibited by preincubation with the other sodium channel blockers and flecainide was more potent than pilsicainide. However, in tracheal strips precontracted with carbachol, the relaxant effects of sodium channel blockers did not differ from each other. TTX, flecainide and pilsicainide did not alter the baseline tension. Preincubation with in-domethacine or L-NAME altered nen-her the post-juctional inhibitory and relaxant effects of the sodium channel blockers nor their inhibitory effects on EFS-induced contractions. In conclusion, all sodium channel blockers used inhibited EFS-induced contractions of the rabbit trac-hea. Flecainide and pilsicainide inhibited carbachol-induced contractions while TTX did not influence them. Pre- and postsynaptic effects of the sodium channel blockers were not changed by in-domethacine or L-NAME.