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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 alpha‐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.