REGIONAL DIFFERENCE IN THE DISTRIBUTION OF L-NAME-SENSITIVE AND L-NAME-INSENSITIVE NANC RELAXATIONS IN CAT AIRWAY

1. To investigate the distribution profile of functional inhibitory no n-adrenergic noncholinergic (i-NANC) nerves and the contribution of NO to the NANC relaxation in the cat, we studied the effects of N-omega- nitro-L-arginine methyl ester (L-NAME) on NANC relaxation elicited by electrical field stimulation (EPS) in the trachea, bronchus and bronch iole. 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) Jr) elicited a monophasic NANC relaxation. By con trast, 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 affe cting the second one. In the trachea, L-NAME (10(-5) M) completely sup pressed the monophasic NANC relaxation when single or short repetitive stimuli (< 5) with 1 ms pulse duration were applied. However, at high er repetitive stimuli (> 10) with 1 or 4 ms pulse duration, suppressio n 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 w hich is sensitive to tetrodotoxin. 4. In the peripheral airway a newly synthesized VIP antagonist (10(-6) M) or a-chymotrypsin (1 U ml(-1)) 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 thidine (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 N O-containing compounds and VIP, are involved in i-NANC neurotransmissi on and the distribution profile of the two components differs in the c entral and peripheral airway of the cat.