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.
Tanaka
H
H
Department of Pharmacology and Anesthesiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Jing
L
L
Takahashi
S
S
Ito
Y
Y
D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D001980:Bronchi / Q000187:drug effects / Q000294:innervation*; D001993:Bronchodilator Agents / Q000494:pharmacology; D002415:Cats; D004594:Electrophysiology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009451:Neuroeffector Junction / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D018408:Patch-Clamp Techniques; D009435:Synaptic Transmission / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000294:innervation*
D001993:Bronchodilator Agents; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester