Mechanism for substance P-induced relaxation of precontracted airway smooth muscle during development

Release of substance P (SP) from sensory nerve endings of the tracheobronch ial system modulates airway smooth muscle contraction and may cause relaxat ion of precontracted airways. We sought to elucidate the effect of postnata l maturation on SP-induced relaxation of precontracted airways and determin e the roles of endogenously generated nitric oxide (NO) and prostaglandins (PGs). Cylindrical airway segments were isolated from the midtrachea of rat s at four different ages, 1, 2, and 4 wk and 3 mo, and contracted to 50-75% of the maximum response induced by bethanechol. SP was then administered i n the absence and presence of the NO synthase inhibitor N-G-nitro-L-arginin e methyl ester (L-NAME), the PG inhibitor indomethacin, or both. Relaxation of airways with SP decreased significantly with advancing postnatal age. S P-induced tracheal relaxation was consistently attenuated by pretreatment w ith L-NAME, indomethacin, or both. In a different group of animals, L-NAME significantly attenuated the relaxant response of airways to PGE(2) exposur e, but indomethacin had no significant effect on the relaxant response to e xogenous NO. We conclude that SP induces a relaxant effect on precontracted airway smooth muscle, which decreases with advancing age and is mediated v ia SP-induced release of NO and/or PG.