ROLE OF ENDOGENOUS NO IN MODULATING AIRWAY CONTRACTION MEDIATED BY MUSCARINIC RECEPTORS DURING DEVELOPMENT

We sought to characterize the role of endogenous nitric oxide (NO) rel eased from airway epithelium in attenuating tracheal smooth muscle (TS M) contraction induced by exposure to acetylcholine (ACh). Organ bath experiments were performed on TSM from young pigs of three ages (3-7 d ays, 2-3 wk, and 3 mo). Concentration-response curves to cumulative do ses of ACh (10(-8) to 10(-4) M) were generated before and after additi on of the NO synthase blocker N-omega-nitro-L-arginine methyl ester (L -NAME). L-NAME caused a significant increase in cholinergic sensitivit y (decrease in 50% effective dose) at 3-7 days and 2-3 wk but not 3 mo . Maximum responses to ACh increased after L-NAME at all three ages. R emoval of tracheal epithelium caused a significant increase in sensiti vity to ACh at all ages, which progressively declined with advancing a ge. In the absence of epithelium, L-NAME no longer influenced contract ile responses to ACh. Density of M-3 muscarinic receptors in tracheal epithelium was upregulated in the youngest piglets. We conclude that, under in vitro conditions, release of endogenous NO opposes cholinergi cally induced contraction of piglet TSM. This phenomenon diminishes wi th advancing postnatal age, requires an intact airway epithelium, and correlates with upregulation of Ms muscarinic receptors in airway epit helium. We speculate that NO may play a useful role in attenuating cho linergically mediated airway smooth muscle contraction in early life w hen pulmonary function is characterized by high airway resistance.