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Hyperoxic exposure enhances airway reactivity in newborn animals, possibly due to altered relaxation. We sought to define the role of prostaglandinand nitric oxide-mediated mechanisms in impaired airway relaxation induced by hyperoxic stress. We exposed 7-day-old rat pups to either room air or hyperoxia (>95% O2) for 7 days to assess airway relaxation and cAMP and cGMP production after electrical field stimulation (EFS). EFS-induced relaxation of preconstricted trachea was diminished in hyperoxic vs. normoxic animals ( P < 0.05). Indomethacin (a cyclooxygenase inhibitor) reduced EFS-induced airway relaxation in tracheae from normoxic ( P < 0.05), but not hyperoxic, rat pups; however, in the presence of NG-nitro-l-arginine methyl ester (a nitric oxide synthase inhibitor) EFS-induced airway relaxation was similarly decreased in tracheae from both normoxic and hyperoxic animals. After EFS, the increase from baseline in the production of cAMP was significantly higher in tracheae from normoxic than hyperoxic rat pups, and this was accompanied by greater prostaglandin E2release only in the normoxic group. cGMP production after EFS stimulation did not differ between normoxic and hyperoxic groups. We conclude that hyperoxia impairs airway relaxation in immature animals via a mechanism primarily involving the prostaglandin-cAMP signaling pathway with an impairment of prostaglandin E2release and cAMP accumulation.

Recent studies suggest that nitric oxide (NO) may act as a chemical messenger in the nervous system. Since neurotransmitters are considered necessary for the sensory function of the carotid body, and molecular O 2 is a co-factor for NO synthesis, we examined whether (a) chemoreceptor tissue also synthesizes NO and if so, (b) does endogenous NO affect chemosensory activity. Experiments were performed on carotid bodies obtained from anesthetized cats ( n = 20 ). Distribution of nitric oxide synthase (NOS), an enzyme that catalyzes the formation of NO was examined using NADPH-diaphorase histochemistry. Many nerve plexuses innervating the chemoreceptor tissue were positive for NADPH-diaphorase, indicating that the nerve fibers are the primary source of NO production in the carotid body. Radiometric analysis of NOS activity of the chemoreceptor tissue averaged 1.94 pmol [ 3 H]citrulline/min/mg protein. NOS activity was significantly less in low pO 2 reaction medium than in room air controls. Chemosensory activity in vitro increased in a dose-dependent manner in response to l -ω-nitro arginine ( l -NNA), an inhibitor of NOS activity. The effects of NOS inhibitor were enantiomer selective as evidence by reversal of the responses by l - but not d -arginine. These observations imply that endogenous NO is inhibitory to carotid body sensory activity. cGMP levels of l -NNA-treated carotid bodies were significantly less than untreated controls, suggesting that the actions of NO are coupled to the cGMP second messenger system, as elsewhere in the nervous system. Based on the findings that (a) low pO 2 decreased NOS activity and, (b) endogenous NO is inhibitory to the sensory discharge, it is suggested that the mechanism(s) of sensory excitation by hypoxia in the carotid body may involve ‘disinhibition’ inhibitory to the sensory discharge, it is suggested that the mechanism(s) of sensory excitation by hypoxia in the carotid body may involve ‘disinhibition’ resulting from NO synthesis.