Nitric oxide mediates the neural nonadrenergic, noncholinergic relaxation of pig tracheal smooth muscle

In pig tracheal smooth muscle, the isometric tension responses to electrical field stimulation (EFS) were studied after raising the tone with carbamylcholine chloride (carbachol). EFS induced frequency-dependent relaxations that were nonadrenergic, noncholinergic (NANC) in nature. Addition of NG-nitro-L-arginine (L-NOArg), an inhibitor of nitric oxide (NO) synthesis from L-arginine, resulted in concentration-dependent inhibition of the relaxation response to EFS. Pretreatment of the tissues with L-arginine (1 mM) prevented the inhibitory effect of L-NOArg on the EFS-induced relaxations at the frequencies studied. However, in the presence of D-arginine, EFS-induced relaxations were inhibited by L-NOArg. L-Arginine, D-arginine, and L-NOArg had no significant effects on basal tone of the muscle. In the presence of L-NOArg, vasoactive intestinal polypeptide (3 x 10(-7) M), the nicotinic agonist dimethylphenyl piperazinium bromide (100 microM), and isoproterenol (1 microM) relaxed carbachol-induced tone. The concentration-dependent selective inhibition of neural relaxation by L-NOArg and its reversal by L-arginine in a stereospecific manner are consistent with NO-mediated NANC relaxation of pig tracheal smooth muscle.