The possible role of nitric oxide in relaxations and excitatory neuroeffector transmission in the cat airway

1. To study the possible role of nitric oxide (NO free radical; NO) or NO-containing compounds in the non-adrenergic, non-cholinergic (NANC) relaxations, we observed the effects of carboxy-2-phenyl-4,4,5,5-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 the effects of C-PTIO on excitatory junction potentials (EJPs), since NO· has a prejunctional action on transmitter release. 2. Nitrosocystine (Cys-NO) (10^-7-10^-3 M) dose-dependently relaxed the bronchial tissue 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 right. 3. Electrical field stimulation (EFS) evoked biphasic NANC relaxations in the small bronchi of the cat. In general, C-PTIO suppressed non-selectively both the first and second components of the NANC relaxations to a similar extent. However, in some bronchial preparations C-PTIO (10^-4 M) selectively suppressed the first component of the NANC relaxation to approximately 50% of the initial value, enhancing the amplitude of the second component of the NANC relaxations. 4. After pretreatment of the bronchial tissues with α-chymotrypsin (1 unit ml^-1) for 30 min in order to inhibit any response to peptides, EFS evoked monophasic NANC relaxation. C-PTIO (10^-5-10^-4 M) dose-dependently 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 initial value. 5. C-PTIO (10^-4 M) enhanced the EJP amplitude evoked by single EFS in the trachea but not in the bronchi. However, C-PTIO enhanced the summation of the EJPs to repeated stimulation to a similar extent in the tracheal and bronchial tissues. Simultaneous application of C-PTIO and L-NAME did not further enhance the summation. 6. These results indicate that NO and NO-containing compounds are involved in the L-NAME-sensitive NANC relaxation in the cat airway, and that only NO. has a prejunctional action which inhibits excitatory neuroeffector transmission.