Developmental Changes in Airway Smooth Muscle Relaxation Mediated by NO and PGE2

Abstract

In this study we investigated changes in relaxation of airways during development and we sought to determine to what extent NO and PGE2 contribute to this response during postnatal maturation. Airway segments were excised from trachea of rats at four different ages (1, 2, and 4 wk and 3 mo). In precontracted tracheal smooth muscle (TSM), electrical field stimulation (EFS) was applied to induce relaxation, in absence or presence of NO synthase (NOS) inhibitor (L‐NAME) or cyclooxygenase inhibitor (indomethacin) or combined. EFS‐induced relaxation of TSM significantly decreased with advancing postnatal age (overall, P < 0.001). The maximal relaxant responses were as follows: at 1wk, 70.2 ± 4.6%; at 2 wk, 55.7 ± 5.2%; at 4 wk, 37.4 ± 4.2% and 3 mo, 22.3 ± 3.7%. Pretreatment with L‐NAME or indomethacin or both, significantly reduced the EFS‐induced relaxation (P < 0.001) compared with controls. Although both inhibitors reduced relaxation, there was a significant difference (P < 0.05) between inhibitors in the extent of relaxation reduce. While at 1 and 2 wk, the relaxation was predominantly reduced by indomethacin, at 3 mo. it was predominated by L‐NAME, whereas there was no difference at 4 wk. We conclude that relaxation of ASM decreases with age and the relaxation mediatory mechanisms alternate during maturation, predominating at by PGE2 at first weeks and replaced by NO at later stages.Supported by Ministry of Health.