Selective autonomic stimulation of canine trachealis with dimethylphenylpiperazinium

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Abstract
The response of canine tracheal muscle to autonomic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) was studied isometrically in 39 dogs in vivo. Intra-arterial (ia) DMPP (2.5 .times. 10-4-2.5 .times. 10-2 mg/kg) caused selective dose-related tracheal contraction [maximum 30.1 .+-. 6.5 gram-force (gf)/cm] due to regional stimulation of parasympathetic ganglia. This contraction was blocked by regional administration of atropine 10-3 mg/kg ia and hexamethonium 5 .times. 10-2 mg/kg ia. Nonselective i.v. administration of DMPP 2.5 .times. 10-2 mg/kg caused parasympathetic tracheal contraction [+13.4 .+-. 1.64 gf/cm] followed by later sympathetic relaxation [-11.8 .+-. 2.3 gf/cm]; 0.5 mg/kg i.v. atropine abolished contraction but did not affect relaxation. The role of the adrenal gland vs. direct sympathetic innervation in producing tracheal relaxation after sympathetic stimulation was also studied. Tracheal relaxation to 2.5 .times. 10-2 mg/kg i.v. DMPP was -18.2 .+-. 4.0 gf/cm before adrenalectomy (ADX) and -4.3 .+-. 0.9 gf/cm afterward (P < 0.001). Tracheal contraction resulting from .alpha.-adrenergic stimulation after 2.5 .times. 10-2 mg/kg i.v. DMPP in .beta.-blocked (BB) dogs was not significantly altered by ADX. At 2.5 .times. 10-1 mg/kg i.v. DMPP, the .alpha.-adrenergic contractile response was still 70% of the response prior to ADX. Apparently, sympathetic tracheal relaxation in dogs is predominantly mediated by circulating catecholamine from the adrenal gland but .alpha.-adrenergic contraction after BB results predominantly from direct sympathetic innervation and is not greatly augmented by adrenal secretion. A new method for selective stimulation of airway cholinergic nerves in vivo without systemic effects is reported.