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 KCl 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.