LIPOXIN A(4) INHIBITS CHOLINERGIC NEUROTRANSMISSION THROUGH NITRIC-OXIDE GENERATION IN THE RABBIT TRACHEA

The effect of lipoxin A(4) and lipoxin B-4 on cholinergic neurotransmi ssion in rabbit tracheal segments was studied under isometric conditio ns in vitro. Lipoxin A(4) attenuated the contractile responses to elec trical field stimulation and caused a rightward shift of the frequency -response curves, so that the stimulus frequency required to produce a half-maximal effect (ES(50)) increased from 8.1+/-0.8 to 25.7+/-1.9 H z (P < 0.001), whereas lipoxin B-4 had no effect. In contrast, lipoxin A(4) did not alter the contractile responses to acetylcholine. Pretre atment of tissues with N-G-nitro-L-arginine methylester inhibited the effect of lipoxin A(4) on electrical field stimulation, but N-G-nitro- D-arginine methylester did not. This inhibition by N-G-nitro-L-arginin e methylester was reversed by L-arginine but not by D-arginine. These results suggest that lipoxin A(4) prejunctionally reduces the vagal ne rve-mediated contraction of airway smooth muscle, probably by inhibiti ng the release of acetylcholine, and that this effect may be exerted t hrough stimulation of nitric oxide generation.