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.
Nault
M A
MA
Department of Physiology, Queen's University, Kingston, ON, Canada K7L 3N6.
Vincent
S G
SG
Fisher
J T
JT
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004285:Dogs; D019344:Lactic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008170:Lung Compliance / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology
D011955:Receptors, Drug; D019344:Lactic Acid; C071423:capsazepine; D002211:Capsaicin