Interaction between halothane and the nonadrenergic, noncholinergic inhibitory system in porcine trachealis muscle

Volatile anesthetics significantly affect cholinergic neural transmission in the airways and relax airway smooth muscle. Activation of the nonadrenergic, noncholinergic inhibitory neural pathway, which is thought to be mediated by nitric oxide, relaxes human and procine airways. The purpose of the current study was to determine in the isolated porcine trachealis muscle whether relaxation of airway smooth muscle by halothane is mediated in part by activation of the nonadrenergic, noncholinergic inhibitory system.

Isometric tension was measured in porcine trachealis muscle suspended in tissue baths in the presence of propranalol (10(-6) M). After stimulation of postsynaptic nicotinic cholinergic receptors with 1,1-dimethyl-4-phenyl-piper-azinium iodide (10(-4) M) to prevent contractile responses to subsequent electrical field stimulation, carbachol (3 x 10(-7) M) was added to increase tone. Nonadrenergic, noncholinergic relaxation responses to electrical field stimulation were then measured in the presence of inhibitors of nitric oxide synthase or L-arginine (the substrate for nitric oxide synthase), in the presence and absence halothane.

Electrical field stimulation produced frequency-dependent relaxations that were attenuated by inhibitors of nitric oxide synthase (NG-nitro-L-arginine methyl ester [L-NAME] or NG-monomethyl-L-arginine, 10(-4) M). Pretreatment with L-arginine (10(-4) M) prevented the effect of L-NAME. Halothane (0.5% or 1.0%) neither enhanced nor attenuated nonadrenergic, noncholinergic relaxations in the presence of L-NAME, D-NAME, L-arginine, or D-arginine.

Halothane, at concentrations < or = 1.0%, does not relax porcine airway smooth muscle in vitro by activating the nonadrenergic, noncholinergic inhibitory system.