THE POSSIBLE ROLE OF NITRIC-OXIDE IN RELAXATIONS AND EXCITATORY NEUROEFFECTOR TRANSMISSION IN THE CAT AIRWAY

1. To structure tile possible role of nitric oxide (NO free radical; N O) or NO-containing compounds in the non-adrenergic, non-cholinergic ( NANC) relaxations, we observed the effects of nyl-4,4,5,S-tetramethyl- imidazoline-1-oxyl-3-oxide (C-PTIO; a newly synthesized NO scavenger) on NANC relaxations in the cat airway. In addition, we also observed t he effects of C-PTIO on excitatory junction potentials (EJPs), since N O has a prejunctional action on transmitter release. 2. Nitrosocystine (Cys-NO) (10(-7)-10(-3) M) dose-dependently relaxed the bronchial tis sue in the presence of 5-HT, atropine and guanethidine and C-PTIO (10( -4) M) shifted the concentration-response curve of the Cys-NO to the r ight. 3. Electrical field stimulation (EFS) evoked biphasic NANC relax ations in the small bronchi of the cat. In general, C-PTIO suppressed non-selectivity both the first and second components of the NANC relax ations to a similar extent. However, in some bronchial preparations C- PTIO (10(-4) hr) selectively suppressed the first component of the NAN C relaxation to approximately 50% of the initial value, enhancing the amplitude of the second component of the NANC relaxations. 4. After pr etreatment of the bronchial tissues with alpha-chymotrypsin (1 unit ml (-1)) for 30 min in order to inhibit any response to peptides, EFS evo ked monophasic NANC relaxation. C-PTIO (10(-5)-10(-4) M) dose-dependen tly suppressed, and at a concentration of 10(-4) M almost halved, the amplitude of NANC relaxation. Additional application of L-NAME further reduced the C-PTIO-resistant NANC relaxation to 20-30 % of the initia l value. 5. C-PTIO (10(-4) M) enhanced the EJP amplitude evoked by sin gle EFS in the trachea but not in the bronchi. However, C-PTIO enhance d the summation of the EJPs to repeated stimulation to a similar exten t in the tracheal and bronchial tissues. Simultaneous application of C -PTIO and L-NAME did not further enhance the summation. 6. These resul ts indicate that NO- and NO-containing compounds are involved in the L -NAME-sensitive NANC relaxation in the cat airway: and that only NO ha s a prejunctional action which inhibits excitatory neuroeffector trans mission.