Inhibitory NANC responses

Inhibitory NANC responses are mediated by both VIP and NO.. NO. partially mediates the airway smooth muscle relaxant effects of VIP in the isolated perfused guinea-pig lung, as NOS inhibitors prevent relaxation induced by VIP but not that induced by isoproterenol (Lilly et al., 1993b). A significant and appropriately timed increase in the NO. content of lung perfusion fluid can be measured in response to VIP (Fig. 7.4). These data support the conclusion that interactions of VIP with NO. products mediate a substantial component of iNANC transmission. In human airways, NOS stimulated as a result of iNANC neurotransmission accounts for a substantial proportion of this relaxant response. Bel-visi and co-workers have shown that the a-chymotrypsin-resistant component of the human iNANC response can be abolished by treatment with NOS inhibitors (Belvisi et al., 1992). 

The activation of NOS or the products thereof modulates airway constrictor responses as well. Atropine-sensitive, electrical field stimulation-induced bronchoconstrictor responses in the guinea-pig are enhanced by NOS inhibitors (Belvisi etal., 1991). Nitrogen oxides also modulate the effects of non-cholinergic bronchoconstrictors. H stimulation of Hi receptors in the guinea-pig lung leads 

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Besides neuropeptides, nitric oxide is an inflammatory mediator in the airways, which is also a vasodilator and a neurotransmitter. Nitric oxide is produced by the enzymatic action of nitric oxide synthetase on L-arginine. Airways contain this enzyme in three different forms, two of which termed neuronal and endothelial nitric oxide synthetase are constitutive whereas the third form called inducible nitric oxide synthetase is inducible. The inflammatory cytokines including IL-1 and TNF-a augment the expression of inducible nitric oxide synthetase in human airway epithelial cells. Nitric oxide causes bronchodilation as a result of the relaxation of bronchial smooth muscles. It has also been suggested that nitric oxide is the neurotransmitter of the inhibitory NANC bronchodilation. The detrimental effects of nitric oxide include airway inflammation and vasodilation. It causes airway edema by increasing the erudition of plasma due to increased blood flow to postcapillary venules. The increased blood flow may also contribute to an increased mucus secretion. The role of nitric oxide in inflammatory responses has not yet been established. 

Todorov S, Pozzoli C, Zamfirova R, Poll E (2003) Prejunctional modulation of non-adrenergic non-cholinergic (NANC) inhibitory responses in the isolated guinea-pig gastric fundus. Neurogastroenterol Motil 15 299-306... 

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