EFFECT OF HYPEROXIA ON SUBSTANCE-P EXPRESSION AND AIRWAY REACTIVITY IN THE DEVELOPING LUNG

This study was undertaken to characterize changes in the tachykinin sy stem induced by hyperoxic exposure and the potential effects on airway contractile responses. We exposed 7-day-old rat pups to either room a ir or hyperoxia (>95% O-2) for 7 days to assess pulmonary beta-preprot achykinin (beta-PPT) gene expression, substance P (SP) levels, and air way contractile responses to cholinergic stimulation before and after neurokinin-1 (NK1) receptor blockade. Lung beta-PPT mRNA expression, l ung and tracheal SP levels, and contractile responses to exogenous ace tylcholine and electrical field stimulation were measured in vitro in normoxia- and hyperoxia-exposed tracheal cylinders. Hyperoxia caused a 1.1- to 2.6-fold increase in steady-state lung beta-PPT mRNA and a 50 and 32% increase in SP levels of lung and trachea, respectively. In r esponse to cholinergic stimulation, maximal contractile force (E-max) of hyperoxia exposed tracheal muscle was significantly higher than for normoxic controls. Addition of the SP (NK1) receptor blocker CP-99994 (10 mu M) decreased sensitivity to electrical field stimulation in bo th hyperoxic and normoxic trachea without a significant decline in E-m ax. These data provide evidence for both increased SP production and e nhanced maximal contractile responses of hyperoxia-exposed neonatal tr achea to cholinergic stimulation. The tachykinin peptide SP does not, however, appear to play a major role in the enhanced airway reactivity associated with hyperoxic lung injury during early postnatal life.