Stretch-Induced Stimulation of Lower Airway Nitric Oxide Formation in the Guinea-Pig: Inhibition by Gadolinium Chloride

Abstract: The effect of stretch on lower airway nitric oxide formation was studied in normoxic tracheostomized anaesthetized guinea-pigs. Increase of level of positive end-expiratory pressure caused increased lower airway nitric oxide formation, as measured by its presence in exhaled tracheal air. The L-type calcium channel blocker, verapamil, did not decrease lower airway nitric oxide formation. Neither the local anaesthetic xylocaine nor the ganglion blocker trimetaphan affected exhaled nitric oxide, excluding local and centrally-mediated neuronal reflexes. Intravenous administration of gadolinium chloride (GdCl₃, 50 mg/kg) induced a rapid and pronounced decrease (75%) in the basal level of exhaled nitric oxide. GdCl₃ completely abolished lower airway nitric oxide formation induced by ventilation with positive end-expiratory pressure (7 cm H₂O). GdCl₃ induced hypoxaemia, but there was no indication for the development of lung oedema. The results indicate that positive end-expiratory pressure stimulates lower airway nitric oxide formation in the guinea-pig. GdCl₃ inhibits lower airway nitric oxide formation in the guinea-pig in vivo, perhaps by interference with stretch-induced cellular calcium-influx.