ROLE OF NITRIC-OXIDE IN NONADRENERGIC, NONCHOLINERGIC RELAXATION AND MODULATION OF EXCITATORY NEUROEFFECTOR TRANSMISSION IN THE CAT AIRWAY

1. The effects of nitrosocysteine (cys-NO), L-N-omega-nitroarginine (L -NNA) and L-N-omega-nitro-L-arginine methylester (L-NAME), oxyhaemoglo bin and Methylene Blue were observed on the resting membrane potential , muscle tone and excitatory junction potentials (EJPs) of cat trachea l smooth muscle tissue. 2. Cys-NO (10(-9) to 10(-6) M) showed no effec t on the resting membrane potential of smooth muscle cells of the cat trachea but it dose-dependently relaxed the tracheal tissue in the pre sence of 5-HT, atropine and guanethidine. 3. Electrical field stimulat ion (EFS) applied during contraction evoked by 5-HT in the presence of atropine and guanethidine evoked non-adrenergic, non-cholinergic (NAN C) muscle relaxation. L-NNA (10(-4) M) and L-NAME (10(-4) M) completel y suppressed the relaxation when single or short repetitive stimuli we re applied, but suppression was incomplete with repetitive stimuli of 4 ms pulse duration applied at 20 Hz. A substantial part of the L-NNA- or L-NAME-insensitive relaxation was abolished by tetrodotoxin. 4. Cy s-NO dose-dependently suppressed the EJPs without changing the resting membrane potential, and L-NNA, L-NAME, Methylene Blue and oxyhaemoglo bin enhanced the amplitude of the EJP to 1.2-1.5 times the control val ue. 5. EJPs showed some summation when repetitive field stimulation wa s applied at 20 Hz. L-NNA or L-NAME enhanced the summation, and the me an slopes were increased from 0.61 +/- 0.22 to 2.0 +/- 0.3, or 1.9 +/- 0.2 mV per stimulus. Vasoactive intestinal polypeptide (VIP) antiseru m and VIP antagonists further enhanced the summation in the presence o f L-NNA. 6. These results indicate that NANC relaxation can he classif ied into two different components according to the threshold for activ ation, and nitric oxide is involved in one. The present results also s uggest that endogenous or exogenous nitric oxide has a prejunctional a ction in inhibiting excitatory neuroeffector transmission in addition to a direct action on the smooth muscle cells, presumably by suppressi ng transmitter release from the vagus nerve.