NITRIC OXIDE (NO) MODULATES CONTRACTILE RESPONSES OF AIRWAY SMOOTH MUSCLE DURING EARLY POSTNATAL LIFE. † 1995

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There are conflicting data on the role of endogenous NO in attenuating airway smooth muscle contraction induced by cholinergic agonists in various adult animal species. We therefore sought to determine whether activation of nitric oxide synthase (NOS) in airway epithelial cells or nerve fibers would modulate tracheal smooth muscle contration induced by acetylcholine (Ach) in young piglets. Tracheal smooth muscle strips were obtained from piglets of two postnatal ages: 3-7 days (n=8) and 2-3 weeks (n=9). After equilibration in an organ bath, tracheal strips were exposed in vitro to increasing concentrations of Ach, before and after blockade of NOS by addition of Nω-Nitro-L-Arginine Methyl Esther (L-NAME) to the bathing medium. Prior administration of L-NAME (18.5 mM) significantly (p<0.5)increased the contractile response to Ach within the first week of life(Fig). A comparable enhancement of Achinduced contraction was observed in response to L-NAME at 2-3 weeks. Removal of epithelium from tracheal strips at both 3-7 and 2-3 wk attenuated the effect of L-NAMEon Ach-induced contraction. We conclude that 1) NO is an important modulator of airway responses to constrictive agents from early in postnatal life, and 2) epithelium is the main source of NO released by exposure to contractile agonists. We speculate that airway epithelial injury in the neonate may remove an important counterbalance to airway constrictor agents.Supp by HL25830 and HL50527

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