1. To investigate the distribution profile of functional inhibitory non-adrenergic noncholinergic (i-NANC) nerves and the contribution of NO to the NANC relaxation in the cat, we studied the effects of NW-nitro-L-arginine methyl ester (L-NAME) on NANC relaxation elicited by electrical field stimulation (EFS) in the trachea, bronchus and bronchiole. 2. EFS applied to the tracheal smooth muscle during contraction induced by 5-HT (10-5 M) in the presence of atropine (10-6 M) and guanethidine (10-6 M) elicited a monophasic NANC relaxation. By contrast, NANC relaxation elicited in the peripheral airway was biphasic, comprising an initial fast followed by a second slow component and L-NAME (10-5 M) selectively abolished the first component without affecting the second one. In the trachea, L-NAME (10-5 M) completely suppressed the monophasic NANC relaxation when single or short repetitive stimuli (< 5) with 1 ms pulse duration were applied. However, at higher repetitive stimuli (> 10) with 1 or 4 ms pulse duration, suppression of NANC relaxation was incomplete. 3. In the small bronchi obtained from L-NAME-pretreated cats, EFS applied during contraction induced by 5-HT (10-5 M) elicited only the slow component of NANC relaxation which is sensitive to tetrodotoxin. 4. In the peripheral airway, a newly synthesized VIP antagonist (10-6 M) or o-chymotrypsin (1 U ml-') considerably attenuated the amplitude of L-NAME -insensitive relaxation.5. Single or repetitive EFS consistently evoked excitatory junction potentials (EJPs) in the central and peripheral airways. When tissues were exposed to atropine (10-6 M) and guanethidine (10-6 M), single or repetitive EFS did not alter the resting membrane potential. 6. These results indicate that at least two neurotransmitters, possibly NO or NO-containing compounds and VIP, are involved in i-NANC neurotransmission and the distribution profile of the two components differs in the central and peripheral airway of the cat.The tracheobronchial smooth muscle is innervated by nerve fibres from cranial parasympathetic outflow and sympathetic trunks (Smith & Taylor, 1971). Recent studies revealed that the cranial parasympathetic nervous system in the airway contains non-adrenergic non-cholinergic (NANC) inhibitory nerves in addition to the well-documented cholinergic excitatory nerve fibres. Furthermore, activation of C-fibre afferent (sensory) nerves induces a number of airway responses including smooth muscle contraction, mucus secretion and plasma exudation through NANC excitatory transmitter (Barnes, 1991

Background: Because eosinophilic airway inflammation is a characteristic feature of bronchial asthma, the treatment of airway inflammation is important in the management of asthma. Theophylline has been reported to reduce airway inflammation, in addition to its well–known bronchodilating effect. Objective: In order to evaluate the effects of theophylline on airway inflammation, we investigated 48 subjects with mild and moderate asthma. Methods: The patients were randomly divided into two groups, with or without theophylline treatment (control n = 24; theophylline, n = 24). We examined the level of serum eosinophil cationic protein (ECP), induced sputum samples, and peak expiratory flow (PEF) and obtained spirograms before and after 4 weeks of treatment with once–daily theophylline (200–600 mg/day) of subjects with mild or moderate asthma. Results: Theophylline significantly increased morning and evening PEF and significantly decreased the diurnal variation of PEF. After treatment with theophylline, both serum ECP and the percentage of eosinophils in induced sputum were significantly decreased. In contrast, peripheral blood eosinophil count was unchanged after treatment with theophylline. Conclusions: These findings suggest that theophylline reduces airway inflammation and the severity of asthma, presumably via suppression of both eosinophil activity and subsequent eosinophil infiltration of the airways.

Nitric oxide (NO), which can be derived from the nervous system or the epithelium of the airway, may modulate airway responsiveness. We investigated how NO derived from the airway nervous system would affect the airway responsiveness to histamine and acetylcholine in mechanically ventilated guinea pigs. An NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (1 mmol/kg i.p.) significantly enhanced airway responsiveness to histamine but not to acetylcholine. Its enantiomer D-NAME (1 mmol/kg i.p.), in contrast, had no effect. The L-NAME-induced airway hyperresponsiveness was still observed in animals pretreated with propranolol (1 mg/kg i.v.) and atropine (1 mg/kg i.v.). Pretreatment with the ganglionic blocker hexamethonium (2 mg/kg i.v.) completely abolished enhancing effect of L-NAME on airway responsiveness. Bilateral cervical vagotomy did not alter the L-NAME-induced airway hyperresponsiveness, whereas sympathetic stellatectomy completely abolished it. Results suggest that NO that was presumably derived from the sympathetic nervous system regulates airway responsiveness to histamine in guinea pigs.

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