Hyperosmolar saline induces airway resistance changes and neuropeptide release: a comparison with the effect of capsaicin, potassium and histamine

BACKGROUND: Healthy subjects do not show any bronchoconstricting response to inhalation of hypertonic saline, in contrast to subjects with symptoms of asthma. There is evidence indicating that these airway reactions may be related to stimulation of sensory nerves. MATERIALS AND METHODS: We investigated the effects of hyperosmolar solutions on the changes in airway resistance as well as on release of neuropeptides from an isolated and perfused guinea pig lung model. RESULTS: We observed that hyperosmolar saline (HS), capsaicin, potassium and histamine induced different patterns of response in airway resistance and neuropeptide release. HS 3.6% induced a biphasic response in airway resistance. Initially a minor relaxation, 4 +/- 1 cmH2O mL-1 min (P < 0.05), followed by a contraction, 22 +/- 3 cmH2O mL-1 min (P < 0.01). This was associated with release of calcitonin gene-related peptide (CGRP) 7.7 +/- 1.9 fmol mL-1 g (P < 0.01), but not of neurokinin A (NKA), a known bronchoconstrictor. Mannitol, at the same osmolarity as HS 3.6%, did not elicit a change in airway resistance, CRGP or NKA release. Capsaicin at 10-6 mol L-1 and potassium at 70 mmol L-1 induced a profound increase in airway tone (50 +/- 9 and 42 +/- 8 cmH2O mL-1 min respectively; P < 0.01) and elevation of both CGRP (6.4 +/- 1.9 and 3.9 +/- 1.1 fmol mL-1 g respectively; P < 0.05) and NKA (3.3 +/- 1.0 and 1.0 +/- 0.2 fmol mL-1 respectively; P < 0.05). Histamine increased the airway resistance by 42 +/- 8 cmH2O mL-1 min (P < 0.01) but had no effect on either CGRP or NKA release. CONCLUSIONS: In healthy guinea pigs, hyperosmolar saline 3.6% initially caused relaxation of the airways followed by contraction and induced release of CGRP-LI. This was not seen with mannitol at the same osmolarity as for the hyperosmolar saline.