Capsaicin and neurokinin A-induced bronchoconstriction in the anaesthetised guinea-pig: evidence for a direct action of menthol on isolated bronchial smooth muscle

Abstract

1. For many years menthol has been used in the treatment of respiratory disorders although, a bronchodilator effect of menthol has yet to be described. Using the bronchoconstrictors capsaicin (acting via stimulating the release of neuropeptides from sensory afferents) and neurokinin A (NKA) we have raised airways resistance in the guinea-pig (GP) and studied the effect of menthol on both capsaicin and NKA-induced bronchoconstriction in vivo. In vitro the effect of menthol on acetylcholine (ACh) and KCl precontracted GP bronchi was also studied.

2. GP (n=13) were anaesthetized (urethane 1.5 g kg⁻¹, i.p.) and a bolus injection of capsaicin (7.5 μg ml⁻¹, i.v.) or infusion of NKA (1 μg min⁻¹, i.v.) was given either in the presence of air (0.81 min⁻¹) or air impregnated with menthol vapour (7.5 μg l⁻¹) freely breathed from a tracheal cannula via a T-piece. Airways resistance (R_aw) and ventilation were measured throughout. Bronchi of mean internal diameter (1029+73.6 μm; n=24) were removed from GP (n=16) and mounted in the Cambustion myograph. Bronchial rings were maximally precontracted with 80 mM KC1 or 2 mM ACh. Relaxation due to a cumulative dose of menthol (1–3000 μM) was measured.

3. Menthol produced a significant (P<0.05) 51.3% reversal of the capsaicin-induced increase in R_aw, and also inhibited the significant (P<0.05) reduction in minute ventilation (V_e) associated with the capsaicin-induced increased in R_aw. Menthol also caused a significant (P<0.05) 41% reversal of the NKA-induced increase in R_aw. The NKA-induced decrease in V_e was again significantly (P<0.05) reversed with menthol inhalation. Menthol caused a significant (P<0.001) dose-dependent relaxation of KCl and ACh precontracted bronchi.

4. We have shown that menthol attenuates both capsaicin and NKA-induced bronchoconstriction in vivo and relaxes KCl and ACh preconstricted bronchi in vitro. Menthol inhibition of NKA and capsaicin-induced bronchoconstriction could be, in part, explained by a direct action of menthol on bronchial smooth muscle.

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