Prostaglandin E2 (PGE2), the major arachidonic metabolite released from tracheal epithelial cells in response to lung injury, induces bronchodilation in low concentration. We tested the hypothesis that prostaglandin-induced relaxation is enhanced during early development and is partly nitric oxide (NO) dependent. Airway segments were isolated from the mid trachea of Sprague Dawley rats at 1 week, 2 weeks and 9 to 12 weeks of age. Following determination of optimal length by electrical field stimulation(EFS), tracheal segments were contracted in vitro to 50-75% of maximum response to bethanechol, prior to PGE2 exposure in the presence or the absence of L-NAME (a nitric oxide synthase inhibitor). There was significant decline in the percent of relaxation of preconstricted airway segments in response to PGE2 with advancing age (Fig). Relaxation response to PGE2 in the first two weeks of age were attenuated in the presence of L-NAME. We conclude that PGE2 induces a relaxant effect on precontracted airway smooth muscle during early maturation via a mechanism involving NO. We speculate that epithelial damage and subsequent reduction in NO release may reduce the bronchodilator response to PGE2 in early postnatal life and predispose to airway hyperreactivity.
Supported by NIH HL 56740.