Role of vagal C-fiber afferents in the bronchomotor response to lactic acid in the newborn dog.
We addressed the hypothesis that vagal C-fiber afferents and cyclooxygenase products are the mechanisms responsible for lactic acid (LA)-induced bronchoconstriction in the newborn dog. Perineural capsaicin and indomethacin were used to block conduction of vagal C fibers and production of cyclooxygenase products, respectively. Perineural capsaicin eliminated (85%) the increase in lung resistance (RL; 45 +/- 5.6%) due to capsaicin (25 microg/kg), whereas the increase in RL (54 +/- 6.9%) due to LA (0.4 mmol/kg) was only inhibited by 37 +/- 4.7% (P < 0.05). Atropine reduced LA-induced bronchoconstriction (42 +/- 2.1%) by an amount similar to that obtained with perineural capsaicin. However, inhibition was significantly increased when atropine was combined with indomethacin (61 +/- 2.7%; P < 0.05), implicating cyclooxygenase products in the LA-induced bronchoconstrictor response. We conclude that the mechanisms responsible for LA-induced bronchoconstriction in the newborn are 1) activation of vagal C-fibers, which, through projections to medullary respiratory centers, leads to activation of vagal cholinergic efferents; 2) production of cyclooxygenase products, which cause bronchoconstriction independent of medullary involvement; and 3) an unknown bronchoconstrictor mechanism, putatively tachykinin mediated. On the basis of our data, pharmaceutical targeting of pulmonary afferents would prevent multiple downstream mechanisms that lead to airway narrowing due to inflammatory lung disease.
Marantz
M J
MJ
Departments of Physiology, Paediatrics, and Anaesthesiology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Vincent
S G
SG
Fisher
J T
JT
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001285:Atropine / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003714:Denervation; D004285:Dogs; D004562:Electrocardiography; D007213:Indomethacin / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology*; D009412:Nerve Fibers / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D009994:Osmolar Concentration; D012129:Respiratory Function Tests; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*
D001993:Bronchodilator Agents; D016861:Cyclooxygenase Inhibitors; D019344:Lactic Acid; D001285:Atropine; D002211:Capsaicin; D007213:Indomethacin