Stimulation of vagal pulmonary C-fibers by a single breath of cigarette smoke in dogs

Lee, Lu-Yuan; Kou, Yu Ru; Frazier, Donald T.; Beck, Eric; Pisarri, T. E.; Coleridge, H. M.; Coleridge, J. C. G.

doi:10.1152/jappl.1989.66.5.2032

Cited by 98 publications

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“…Taken together, nicotine contained in the cigarette smoke exerts a direct stimulatory effect on both C-fiber afferents and RARs in the lungs (13)(14)(15)(16); the effect is more pronounced and consistent on the former. The electrophysiologic evidence further suggests the presence of acetylcholine nicotinic receptors on the membrane of sensory terminals of these lung afferents (13,16). The finding that nicotine is responsible for the smoke-evoked irritant effects on airway afferents was later confirmed in a study on healthy human volunteers when the intensity and detection of the airway irritation were measured using a psychophysical technique (7).…”

Section: Airway Afferents Involved In the Reflex Responses To Inhaledmentioning

confidence: 82%

“…The delayed response developed 10-20 sec after the smoke inhalation and was caused by nicotine-induced bronchoconstriction, mediated through the cholinergic reflex (16). Taken together, nicotine contained in the cigarette smoke exerts a direct stimulatory effect on both C-fiber afferents and RARs in the lungs (13)(14)(15)(16); the effect is more pronounced and consistent on the former. The electrophysiologic evidence further suggests the presence of acetylcholine nicotinic receptors on the membrane of sensory terminals of these lung afferents (13,16).…”

Section: Airway Afferents Involved In the Reflex Responses To Inhaledmentioning

confidence: 92%

“…This response was found in approximately 90% of the fibers tested, and was independent of the bronchoconstrictive effect of the smoke. Furthermore, nicotine contained in the cigarette smoke is responsible for generating this stimulatory effect because it can be completely blocked by pretreatment with hexamethonium, the acetylcholine nicotinic receptor antagonist (13). On the other hand, Sellick and Widdicombe (14) reported the first evidence that cigarette smoke stimulates RARs in rabbit lungs.…”

Section: Airway Afferents Involved In the Reflex Responses To Inhaledmentioning

confidence: 99%

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Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Lee

Widdicombe

2001

Environ Health Perspect

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Among the three major types of sensory receptors innervating the airways and lungs, C-fiber endings and rapidly adapting pulmonary receptors (RARs or irritant receptors) are believed to be primarily responsible for eliciting the reflex responses in defending the lungs against inhaled irritants and toxins (1-3). The third type, slowly adapting pulmonary receptors (SARs or stretch receptors), plays an important role in regulating the respiratory volume-timing relationship (4), and is considered to be pure mechanoreceptor and relatively insensitive to chemical irritants. Several recent studies have attempted to uncover the mechanisms underlying the interaction between the pulmonary C fibers and RARs in the overall regulation of the defense reflex responses. Inhalation of cigarette smoke, a common inhaled irritant in human airways, has been shown to elicit irregular breathing pattern, cough reflex, and bronchoconstriction in a number of species including humans (5-9). Although it is believed that most of these responses are mediated through the activation of these two types of vagal afferents, the relative contributions of these two types of afferents to the emergence of these reflex responses are not known. In anesthetized animals (dogs, cats, or rats), spontaneous inhalation of one to two tidal breaths of cigarette smoke into the lungs via a tracheal cannula immediately elicited pulmonary chemoreflexes, characterized by apnea, bradycardia, and hypotension, known to be elicited by activation of pulmonary C fibers (1-3,6). After perineural capsaicin treatment of both cervical vagi to selectively block the conduction of capsaicin-sensitive C fibers, inhaled cigarette smoke no longer evoked any inhibitory effect on breathing (9). Conversely, an augmented inspiration, a reflex effect of activating RARs, was triggered within the first three breaths from the onset of cigarette smoke inhalation in > 85% of the rats studied (Figure 1). When the temperature of the vagus nerve was cooled progressively to 6-7 °C to block the conduction of myelinated afferents, as indicated by the ablation of the apneic response to lung inflation, the augmented breaths evoked by the cigarette smoke inhalation were also abolished (9). Both the apnea and augmented breath evoked by inhaled cigarette smoke were completely abolished by bilateral cervical vagotomy. Similarly, augmented breaths were also elicited when other chemical irritants such as sulfur dioxide (SO 2 ) (9), ammonia (NH 3 ) (9), acrolein (10), and wood smoke (11) were inhaled after the perineural capsaicin treatment of both vagi in anesthetized rats.It is interesting to note that augmented breaths were consistently elicited by inhaled irritants only after the conduction in bronchopulmonary C-fiber afferents are blocked by perineural capsaicin treatment of both vagi but were rarely seen when the same irritants were inhaled in the same animals with intact C fibers (9-11). These results suggest that both vagal bronchopulmonary C-fiber afferents and RARs are stimulated by these inhale...

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Section: Airway Afferents Involved In the Reflex Responses To Inhaledmentioning

confidence: 82%

Section: Airway Afferents Involved In the Reflex Responses To Inhaledmentioning

confidence: 92%

Section: Airway Afferents Involved In the Reflex Responses To Inhaledmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Lee

Widdicombe

2001

Environ Health Perspect

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“…Several studies have demonstrated that SP is a proinflammatory agent that influences various signaling transduction pathways within a complex inflammatory network by C-fiber afferent stimulation following external stimulation (1,4,9,14,22). In vivo studies have demonstrated the efficacy of antioxidants and free radical scavengers in ameliorating increases in endogenous SP levels (which may result in increased microvascular permeability via upregulated ICAM-1 expression, edema, and severe hypoxia) (11).…”

Section: Discussionmentioning

confidence: 99%

Substance P acts via the neurokinin receptor 1 to elicit bronchoconstriction, oxidative stress, and upregulated ICAM-1 expression after oil smoke exposure

Li¹,

Chen²,

Chang³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Li P-C, Chen W-C, Chang L-C, Lin S-C. Substance P acts via the neurokinin receptor 1 to elicit bronchoconstriction, oxidative stress, and upregulated ICAM-1 expression after oil smoke exposure. Am J Physiol Lung Cell Mol Physiol 294: L912-L920, 2008. First published March 7, 2008 doi:10.1152/ajplung.00443.2007.-This study aimed to 1) assess whether substance P (SP) acts via neurokinin (NK)-1 and NK-2 receptors to stimulate neurogenic inflammation (indicated by formation of ICAM-1 expression and oxidative stress) following oil smoke exposure (OSE) in rats; and 2) determine if pretreatment with antioxidants ameliorates the deleterious effects of OSE. Rats were pretreated with NK-1 receptor antagonist CP-96345, NK-2 receptor antagonist SR-48968, vitamin C, or catechins. OSE was for 30 -120 min. Rats were killed 0 -8 h later. Total lung resistance (RL), airway smooth muscle activity (ASMA), lung ICAM-1 expression, neurogenic plasma extravasation (via India ink and Evans blue dye), bronchoalveolar lavage fluid SP concentrations, and reactive oxygen species formation [via lucigenin-and luminalamplified chemiluminescence (CL)] were assessed. Lung histology was performed. SP concentrations increased significantly in nonpretreated rats following OSE in a dose-dependent manner. RL and total ASMA increased over time after OSE. Vitamin C and catechin pretreatments were associated with significantly reduced lucigenin CL 2 and 4 h after OSE. Pretreatment with catechins significantly reduced luminal CL counts 4 and 8 h after OSE. Evans blue levels were significantly reduced following 60 and 120 min of OSE in catechinand CP-96345-pretreated rats. ICAM-1 protein expression was significantly decreased in all pretreatment groups after OSE. Thickening of the alveolar capillary membrane, focal hemorrhaging, interstitial pneumonitis, and peribronchiolar inflammation were apparent in OSE lungs. These findings suggest that SP acts via the NK-1 receptor to provoke neurogenic inflammation, oxidative stress, and ICAM-1 expression after OSE in rats.reactive oxygen species; intracellular adhesion molecule-1; acute lung injury ACTIVATION OF NONMYELINATED bronchopulmonary C-fiber endings by various stimuli [including cigarette smoke (9), airway surface osmolality changes (14), and fire smoke (22)] causes the release of tachykinins and calcitonin gene-related peptide neuropeptides stored in the peripheral nerve terminals, eliciting both central nervous system (CNS) and local axon reflex responses (4). The CNS reflex consists of bronchoconstriction, expiratory apnea, rapid shallow breathing, cough, hypotension, and bradycardia, whereas the axon reflex response initiates local inflammation, increased mucous secretion, and bronchoconstriction. Substance P (SP), a tachykinin neuropeptide, induces a range of neuroimmunogenic effects on target smooth muscle or parasympathetic ganglia cells expressing neurokinin (NK)-1 or NK-2 receptors (1, 2). These effects, collectively termed neurogenic airway inflammation, comprise bronchoconstriction, microvasc...

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“…Afferent activity arising from the lung vagal sensory receptors was recorded by using techniques described elsewhere (24). Briefly, the left vagus nerve was left intact, whereas the right vagus nerve was sectioned.…”

Section: Methodsmentioning

confidence: 99%

The involvement of hydroxyl radical and cyclooxygenase metabolites in the activation of lung vagal sensory receptors by circulatory endotoxin in rats

Lai

Ruan

Kou

2005

Journal of Applied Physiology

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The involvement of hydroxyl radical and cyclooxygenase metabolites in the activation of lung vagal sensory receptors by circulatory endotoxin in rats. J Appl Physiol 98: 620 -628, 2005. First published October 1, 2004; doi:10.1152/japplphysiol.00539.2004.-Circulatory endotoxin can stimulate vagal pulmonary C fibers and rapidly adapting receptors (RARs) in rats, but the underlying mechanisms are not clear. We investigated the involvement of hydroxyl radicals and cyclooxygenase metabolites in the stimulation of C fibers and RARs by circulatory endotoxin (50 mg/kg) in 112 anesthetized, paralyzed, and artificially ventilated rats. In rats pretreated with the vehicle, endotoxin stimulated C fibers and RARs and caused a slight increase in total lung resistance (RL) and a decrease in dynamic lung compliance. In rats pretreated with dimethylthiourea (a hydroxyl radical scavenger) alone, indomethacin (a cyclooxygenase inhibitor) alone, or a combination of the two, C-fiber and RAR responses [C fiber: change (⌬) ϭ Ϫ62, Ϫ79, and Ϫ85%; RAR: ⌬ ϭ Ϫ80, Ϫ84, and Ϫ84%, respectively] were reduced, and the RL response was prevented. The suppressive effects of a combination of dimethylthiourea and indomethacin on the C-fiber and RAR responses were not superior to indomethacin alone. In rats pretreated with isoproterenol (a bronchodilator), the C-fiber response was not significantly affected (⌬ ϭ Ϫ26%), the RAR response was reduced (⌬ ϭ Ϫ88%), and the RL response was prevented. None of these pretreatments affected the dynamic lung compliance response. These results suggest that 1) both hydroxyl radicals and cyclooxygenase metabolites are involved in the endotoxin-induced stimulation of C fibers and RARs, and 2) the involvement of these two metabolites in the C-fiber stimulation may be due to their chemical effects, whereas that in the RAR stimulation may be due to their bronchoconstrictive effects. pulmonary C fibers; rapidly adapting receptors; reactive oxygen metabolites ENDOTOXEMIA CAUSES TACHYPNEA, leading to hyperventilation in septic shock patients (3, 4), but the causes are not completely understood. The tachypnea induced by circulatory endotoxin in rats is prevented by bilateral cervical vagotomy, suggesting that it is a vagally mediated respiratory reflex (42). Electrophysiological studies in rats have revealed that lung C-fiber nerve endings (C fibers) and pulmonary rapidly adapting receptors (RARs), two major types of lung vagal sensory receptors, are activated by circulatory endotoxin (21). Both lung C fibers and RARs play an important role in the detection of pulmonary pathophysiological conditions and eliciting resultant respiratory reflexes (9,25,40). The physiological characteristics of these two types of lung receptors are different (9,25,40). For example, lung C fibers are very sensitive to chemical stimuli (e.g., chemical mediators) but relatively insensitive to mechanical stimuli (e.g., bronchoconstriction). In contrast, RARs can be stimulated by chemical mediators and/or changes in lung mechanics. The mechanisms...

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Stimulation of vagal pulmonary C-fibers by a single breath of cigarette smoke in dogs

Cited by 98 publications

References 0 publications

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Substance P acts via the neurokinin receptor 1 to elicit bronchoconstriction, oxidative stress, and upregulated ICAM-1 expression after oil smoke exposure

The involvement of hydroxyl radical and cyclooxygenase metabolites in the activation of lung vagal sensory receptors by circulatory endotoxin in rats

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