Role of vagal C-fiber afferents in the bronchomotor response to lactic acid in the newborn dog

Abstract

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.

Identification and properties of parietal pleural afferents in rabbits

“…The effects of capsaicin on unmyelinated afferents in the vagus nerve (Coleridge et al 1965; Kaufman et al 1982; Solway & Leff, 1991; Marantz et al 2001; Kollarik et al 2003; Lee et al 2003) and also the limb muscle (Dousset et al 2004; Hoheisel et al 2004) and the diaphragmatic afferents (Hussein et al 1990) are well documented. In all the aforementioned studies capsaicin was injected into the general circulation at lower concentrations (10 −7 –10 −8 m ) than in our study (10 −5 m ).…”

Perivagal antagonist treatment in rats selectively blocks the reflex and afferent responses of vagal lung C fibers to intravenous agonists

“…Perivagal capsaicin treatment has been widely used as an intervention to study the role of vagal lung C fibers in eliciting reflex changes in breathing patterns (9,28,33,43,49), in reflex bronchoconstriction (34,48), and in airway hypersensitivity (17,18) using whole animal models. Capsaicin, a chemical extracted from hot peppers, is an agonist targeting TRPV1 receptors (29).…”

“…Capsaicin, a chemical extracted from hot peppers, is an agonist targeting TRPV1 receptors (29). When capsaicin is applied perineurally to the vagus nerves, the treatment blocks the neural conduction of vagal C fibers (40,52) and C-fiber-mediated airway responses (9,17,18,33,34,43,48,49). However, perivagal capsaicin treatment cannot be used to delineate the specific types of pharmacological receptors involved, because it nonselectively prevents airway responses resulting from activation of a number of different types of pharmacological receptors located at vagal lung C-fiber terminals (33,43,49).…”

Afferent vagal pathways mediating respiratory reflexes evoked by ROS in the lungs of anesthetized rats

“…To differentiate the roles of lung C fibers and RARs in evoking airway reflexes, several techniques for producing differential vagal blockages have been employed. For instance, perineural application of capsaicin, a chemical extracted from hot peppers, to both cervical vagi has been shown to selectively block the airway reflexes resulting from stimulation of lung C fibers (23,26,32). On the other hand, the cooling of both cervical vagi to 6-7°C has been demonstrated to differentially block airway reflexes originating from stimulation of lung myelinated afferents (23,28).…”