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

1997; Wiley; Volume: 121; Issue: 8 Linguagem: Inglês

10.1038/sj.bjp.0701319

1476-5381

Caroline Wright, E.A. Laude, T. J. Grattan, Alyn H. Morice,

Ion channel regulation and function

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. 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 m M KC1 or 2 m M ACh. Relaxation due to a cumulative dose of menthol (1–3000 μ M ) was measured. 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. 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. British Journal of Pharmacology (1997) 121 , 1645–1650; doi: 10.1038/sj.bjp.0701319