Participation of endogenous nitric oxide in the effect of hypoxia in vitro on neuro-effector transmission in guinea-pig ileum.

The implication of endogenous nitric oxide in the effect of hypoxia on the neurotransmission in the enteric nervous system of guinea-pig ileum was studied in vitro. Three methodological approaches have been used: (i) Stretch-induced phases of peristaltic reflex in ileal segments; (ii) twitch contractions of longitudinal segments, evoked by electrical field stimulation; and (iii) release of [3H]acetylcholine from longitudinal muscle-myenteric plexus preparations, measured by liquid spectrophotometry. The effect of nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 100 microM) was studied under normoxic conditions. L-NNA did not change significantly the ascending contraction phase of peristaltic reflex and the amplitude of twitch contractions. However, the same concentration of L-NNA increased the stimulation-evoked acetylcholine release. The descending relaxation phase decreased in the presence of L-NNA. In another set of experiments, hypoxia was mimicked by replacement of oxygen from the perfusion medium with nitrogen for a period of 30 min. Hypoxia significantly decreased the ascending contraction phase, the twitch contractions, and the release of acetylcholine from the myenteric plexus. Under hypoxic conditions, pretreatment with L-NNA did not change either the contractile responses, nor the release of acetylcholine. Our results suggest that under conditions of oxygen deprivation, endogenous nitric oxide seems to be inefficient in modulating the cholinergic neurotransmission in guinea-pig ileum.