Cholinergic and nonadrenergic mechanisms in human and guinea pig airways

Electrical field stimulation (70 V, 1 ms, 0.2-500 Hz) of human bronchial strips and guinea pig tracheal chains produced contractile and relaxant responses. Contractions were blocked by atropine, 10(-6) M, and tetrodotoxin (TTX), 0.1-1.0 micrograms/ml, demonstrating a cholinergic excitatory neural component. Frequencies causing half-maximal contractile response to field stimulation (EFc 50) were 10 +/- 2 Hz for guinea pig and 13 +/- 1 Hz for human airways. Relaxations were unmasked by atropine 10(-6) M and slightly diminished by propranolol in guinea pig but not human airways, demonstrating a predominantly nonadrenergic inhibitory pathway in both species. Relaxation of intrinsic tone occurred at stimulation frequencies of 1 Hz or more. Frequencies causing half-maximal relaxation (EFi 50) were 3.5 +/- 0.3 Hz for guinea pig trachealis and 38 +/- 6 Hz for human bronchi. Following 1 microgram/ml TTX, EFi 50 values increased to 104 +/- 12 and 70 +/- 14 Hz, respectively. Frequencies of field stimulation that were inhibitable by TTX (less than or equal to 20 Hz) induced greater relaxation in guinea pig than human airways (70 vs. 10% of the maximal relaxation to 10(-2) M theophylline, respectively). The methods of analysis outlined in this study can be used to compare relative degrees of functional innervation between tissues from the same or different species.