Hematin supplementation protects against hyperoxia‐induced airway hyperresponsiveness (870.8)

Abstract

It was shown that neonatal hyperoxic‐exposure associates with airway hyperresponsiveness and impaired nonadrenergic noncholinergic relaxation. Previously we have demonstrated the ability of endogenous carbon monoxide (CO) to normalize the airway relaxation under hyperoxic conditions. The aim of this study was to investigate the effect of CO on the hyperoxia‐induced airway hyperresponsiveness. Tracheal cylinders were excised from rat pups 12 days old, exposed to hyperoxia or room air for seven days. Electrical field stimulation (EFS) was applied to induce contraction. The preparations were supplemented with CO precursor ‐ hematin in presence or absence of heme oxygenase (HO) inhibitor tin protoporphyrin‐IX (SnPP‐IX; 100 µM), and/or soluble guanylyl cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a] quinoxalin‐1‐one (ODQ; 10 µM). In TSM obtained from hyperoxia‐exposed animals the contractile responses were increased significantly as compared to room air‐exposed animals, but supplementation of tissues with hematin reversed the contractile responses in hyperoxic group to almost normal level. Inhibiton of HO by SnPP‐IX diminished this effect of hematin. Similar effect was shown also by ODQ alone or in combination with SnPP‐IX. We conclude that increase of CO production overcomes the effects of hyperoxia on airway contractile responses via cGMP signaling and this may serve as a therapeutic approach for treatment of increased airway reactivity in hyperoxia‐exposed neonates.