S-nitrosoglutathione breakdown prevents airway smooth muscle relaxation inthe guinea pig

Airway levels of the endogenous bronchodilator S-nitrosoglutathione (GSNO) are low in children with near-fatal asthma. We hypothesized that GSNO could be broken down in the lung and that this catabolism could inhibit airway s mooth muscle relaxation. In our experiments, GSNO was broken down by guinea pig lung homogenates, particularly after ovalbumin sensitization (OS). Two lung protein fractions had catabolic activity. One was NADPH dependent and was more active after OS. The other was NADPH independent and was partiall y inhibited by aurothioglucose. Guinea pig lung tissue protein fractions wi th GSNO catabolic activity inhibited GSNO-mediated guinea pig tracheal ring relaxation. The relaxant effect of GSNO was partially restored by aurothio glucose. These observations suggest that catabolism of GSNO in the guinea p ig 1) is mediated by lung proteins, 2) is partially upregulated after OS, a nd 3) may contribute to increased airway smooth muscle tone. We speculate t hat enzymatic breakdown of GSNO in the lung could contribute to asthma path ophysiology by inhibiting the beneficial effects of GSNO, including its eff ect on airway smooth muscle tone.