Sites of nitric oxide (NO) actions in control of circular muscle motility of the perfused isolated canine ileum

In the isolated intra-arterially perfused canine ileum, N omega -nitro-L-arginine (L-NNA, 3 x 10(-4) M) increased tonic and phasic motor activity of the circular muscle. As has previously been shown, L-NNA enhanced contractions to electrical field stimulation at sites proximal to the serosal electrodes and converted initial relaxation when present at distal sites to contraction. L-NNA shifted the acetylcholine dose-response curve to the left and amplified the response to low-dose acetylcholine. Following L-NNA, addition of 10(-5) M sodium nitroprusside (NO donor) returned the tonic and phasic activity, the electrical field stimulation responses, and the acetylcholine dose-response curve to control values. Tetrodotoxin (TTX, 10(-6) M) increased tone (less than L-NNA) and abolished responses to both electrical field stimulation and motor activity induced by prior L-NNA. Subsequent L-NNA did not alter TTX-induced tonic motor responses. TTX also shifted the acetylcholine dose-response curve leftward and increased the responses to low-dose acetylcholine. After TTX, sodium nitroprusside returned the low-dose acetylcholine responses to control values and, after L-NNA, failed to restore them to control values. After L-NNA and TTX, sodium nitroprusside restored responses to low-dose acetylcholine to control values, Thus, removal of inhibition of the release of excitatory neurotransmitters, not removal of actions of NO on the muscle, accounted for the increases in tonic and phasic activity from L-NNA. Uninhibited release of excitatory transmitters augmented circular muscle responses to low-dose acetylcholine. TTX eliminated effects of excitatory transmitters, allowing exogenous NO to reduce low-dose acetylcholine contractions. No treatment affected the maximum responses to acetylcholine, produced by a contractile mechanism independent of muscle excitability and unaffected by exogenous NO or release of neurotransmitters.