EFFECT OF HYPEROSMOLARITY ON HUMAN ISOLATED CENTRAL AIRWAYS

1 We studied the effect of hyperosmolarity on human isolated airways because a better understanding of the effect of hyperosmolarity on the human airway wall may improve insight into the pathophysiology of hyperosmolarity-induced bronchoconstriction in asthma. 2 In cartilaginous bronchial rings dissected from fresh human lung tissue, hyperosmolar Krebs-Henseleit buffer (450 mosM, extra sodium chloride added) evoked a biphasic response: a rapid relaxation phase (peak after 5.0 +/- 0.3 min) followed by a slow contraction phase (peak after 25.4 +/- 0.8 min). 3 With the histamine (H1) receptor antagonist mepyramine, the contraction phase was reduced to 41.2% of the control value (P < 0.001), with atropine to 50.0% (P < 0.01), with the local anaesthetic lignocaine to 48.7% (P < 0.05) and with mepyramine together with atropine to 19.2% (P < 0.001). 4 With the inhibitor of neutral metalloendopeptidase, phosphoramidon, the contraction phase increased to 128.0% of the control value (P < 0.05) and after removal of the epithelium to 131.8% (P < 0.05). 5 Indomethacin, the leukotrine C4/D4 (LTC4/D4) antagonist FPL 55712 or the blocker of nerve conduction tetrodotoxin, had no effect on the contractile phase. 6 The relaxation phase was not altered by any of these drugs nor by epithelial denudation. The relaxation phase was also unchanged in the presence of alpha-chymotrypsin, which degrades muscle relaxing peptides such as vasoactive intestinal peptide. 7 Hypersomolar buffer slightly increased the sensitivity and maximal response to methacholine as well as the cholinergic twitch to electric field stimulation. 8 We conclude that hyperosmolarity releases acetylcholine, histamine and neuropeptides in the human airway wall in sufficient quantities to contract airway smooth muscle. This release itself or its effect on airway muscle is modulated by the airway epithelium. The mechanism of the relaxation phase may be an unknown smooth muscle relaxing substance or a direct effect on the airway muscle, related to ion fluxes.