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Mechanisms of capsaicin‐ and lactic acid‐induced bronchoconstriction in the newborn dog

1 Capsaicin activation of the pulmonary C fibre vanilloid receptor (VR1) evokes the pulmonary chemoreflex and reflex bronchoconstriction. Among potential endogenous ligands of C fibre afferents, lactic acid has been suggested as a promising candidate. We tested the hypotheses that (a) lactic acid behaves as a stimulant of C fibre receptors in the newborn dog to cause reflex bronchoconstriction, and (b) lactic acid causes reflex bronchoconstriction via the same pulmonary C fibre receptor mechanism as capsaicin using the competitive capsaicin/VR1 receptor antagonist capsazepine. 2 Right heart injection of lactic acid caused a significant increase (47 ± 8.0%) in lung resistance (RL) that was atropine sensitive (reduced by 75%; P < 0.05), consistent with reflex activation of muscarinic efferents by stimulation of C fibre afferents. 3 Infusion of the competitive capsaicin antagonist capsazepine caused an 80% reduction (P < 0.01) in the control bronchoconstrictor response (41 ± 8.5% increase in RL) to right heart injections of capsaicin. The effects of capsazepine are consistent with reversible blockade of the VR1 receptor to abolish C fibre‐mediated reflex bronchoconstriction. 4 Lactic acid‐evoked increases in RL were unaffected by VR1 blockade with capsazepine, consistent with a separate lactic acid‐induced reflex mechanism. 5 We conclude that (a) putative stimulation of C fibres with lactic acid causes reflex bronchoconstriction in the newborn dog, (b) capsazepine reversibly antagonizes reflex bronchoconstriction elicited by right heart injection of capsaicin, presumably by attenuating capsaicin‐induced activation of the C fibre ‘capsaicin’ receptor (VR1), and (c) capsazepine resistance of lactic acid‐induced bronchoconstriction indicates that lactic acid evokes reflex bronchoconstriction by a separate mechanism, possibly via the acid‐sensing ionic channel.