Airway endothelin levels in asthma, influence of endobronchial hypertonic saline challenge

Background The pathophysiology of exercise-induced asthma is not well under stood. Hypertonicity of the airway lining fluid resulting from loss of wate r due to hyperventilation is considered to play a role, but the precise mec hanism by which hypertonicity can induce bronchoconstriction is unknown. Pe ptides of the endothelin (ET) family have potent smooth muscle contractile properties, and have been linked to airway narrowing in stable asthma. We p ostulated that ET release may contribute to the acute bronchoconstrictor re sponse induced by a hypertonic stimulus. Methods Seven male asthmatic subjects underwent local endobronchial challen ge with hypertonic (3.6%) saline and, as a control, isotonic (0.9%) saline aerosols in separate bronchopulmonary segments. Bronchoalveolar lavage (BAL ) was performed at both sites during the phase of immediate bronchoconstric tion. Concentrations of immunoreactive ET and of the mast cell products, hi stamine, tryptase and prostaglandin D-2, in BAL fluid were measured. Results Concentrations of ET in BAL fluid from the hypertonic saline-challe nged sites were significantly lower than those in BAL fluid from sites expo sed to isotonic saline (0.19 [0.1 1-1.24] fmol/mL vs 0.40 [0.20-2.36] fmol/ mL, P < 0.05). Concentrations of histamine, tryptase, and prostaglandin D-2 did not differ significantly between the two sites. Conclusions These findings do not support the hypothesis that ET release wi thin the airway lumen is involved in the bronchoconstrictor response induce d by hypertonic saline.