L-NAME-sensitive and -insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro.

The neurotransmitters responsible for neurogenic airway relaxation are still unknown. We investigated the effects of N omega-nitro-L-arginine methylester (L-NAME) on nonadrenergic and noncholinergic (NANC) relaxation evoked by electrical stimulation of vagus nerves in vivo and in vitro in cat. To that end, we measured pulmonary resistance during vagal nerve stimulation (VS) in vivo, and isometric tension of small bronchi (1-3 mm outer diameter) during electrical field stimulation (EFS) in vitro. During infusion of 5-hydroxytryptamine (5-HT), VS transiently decreased total pulmonary resistance in the presence of atropine and propranolol, with peak relaxation at several seconds after the VS and a gradual return to baseline within 2-3 min. L-NAME abolished the initial peak relaxation and reduced the peak amplitude, but did not affect the duration of the NANC relaxation. In small bronchi obtained from control cats, EFS evoked a biphasic NANC relaxation, comprising an initial fast component followed by a second slow component, and L-NAME (10(-5) M) selectively abolished the first component without affecting the second. Whilst in the small bronchi obtained from L-NAME pretreated cats, EFS elicited only the slow component of NANC relaxation, which was insensitive to L-NAME but sensitive to tetrodotoxin. These results indicate that nonadrenergic noncholinergic relaxation induced by vagal nerve stimulation during infusion of 5-hydroxytryptamine can be classified into two components, and that at least two neurotransmitters, including nitric oxide, are involved in the relaxation.