Effects of n-omega-nitro-l-arginine methyl-ester (l-name) and treatment of guinea-pigs with lipopolysaccharide (LPS) on neurogenic tension responses of tracheal strips.
The role of nitric oxide in neurogenic contractile and relaxant responses of specific pathogen-free guinea-pig airways was examined by studying the effects of the nitric oxide synthase (NOS) inhibitor, L-NAME, and of treatment of animals with LPS to induce NOS. Tracheal strips under isometric conditions were left under basal force or were contracted with 3 x 10(-7) M methacholine. Field stimulation (0.3 - 30 Hz; 0.5 msec; 130 V; 10 sec trains) was administered to obtain tetrodotoxin-sensitive multi-phasic responses consisting of contraction followed by relaxation. In the presence of L-NAME (10(-4) M) the contractile phase was potentiated but the relaxation phase was not inhibited. This finding does not support the hypothesis that nitric oxide is an important NANC-I neurotransmitter in the guinea-pig trachea. After treatment of animals with LPS (E. coli; one i.p. injection, 4 mg/kg, 4 days before use) to induce NOS, there was no effect on the contraction or relaxation to field stimulation. In strips prepared from LPS-treated animals, L-NAME again did not inhibit the relaxation phase but did potentiate the contraction phase. These findings suggest that nitric oxide modulates excitatory neural-induced responses in the trachea, but has little neurotransmitter role per se.
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