Abstract 1839 Pulmonary: Reactive Airway Diseases I Poster Symposium, Monday, 5/3
Non-adrenergic non-cholinergic (NANC) innervation plays an important role in the modulation of airway relaxation by release of different neurotransmitters including nitric oxide (NO). It has been previously shown that the NANC inhibitory system matures with age in rabbits. Because EFS activates the NANC inhibitory pathway we sought to investigate the role of NO in EFS-induced relaxation of precontracted airways at different ages. Airway segments of 3 mm were isolated from the mid trachea of 2, 4, 6 and 12 week old mice and precontracted in vitro to 50-75% of maximum induced by bethanecol. EFS at 0.5 to 64 Hz was then performed in the absence and presence of the NO synthase inhibitor (L-NAME). The percentage of relaxation of precontracted tracheal segments increased significantly with advancing age. At 64 Hz EFS induced a relaxation of 18±5% at 2 weeks, 49±12% at 4 weeks, 73±9% at 6 weeks. The % relaxation of trachea to EFS did not differ between 6 and 12 weeks. L-NAME partially inhibited EFS-induced relaxation of airways at 12 weeks (from 70±6% to 40±12% at 64 Hz), and almost abolished tracheal relaxation induced by lower EFS frequencies at 4 weeks. We conclude that there is a maturational increase in the EFS-induced relaxation of precontracted trachea in mice, which is partly mediated by NO. We speculate that NO may play a greater role in inducing airway smooth muscle relaxation in early postnatal life, with later maturation of non NO mediated mechanisms modulating airway reactivity.
Supported by NIH HL: 56470 and 50527.