Ozone enhances excitabilities of pulmonary C fibers to chemical and mechanical stimuli in anesthetized rats

1998 ◽  
Vol 85 (4) ◽  
pp. 1509-1515 ◽  
Author(s):  
Ching-Yin Ho ◽  
Lu-Yuan Lee
Keyword(s):  
Low Dose ◽  
Acute Exposure ◽  
Right Atrial ◽  
Mechanical Stimuli ◽  
Lung Inflation ◽  
C Fibers ◽  
Arterial Blood ◽  
Baseline Activity ◽  
Tracheal Pressure ◽  
C Fiber

Acute exposure to ozone (O3) enhances pulmonary chemoreflex response to capsaicin, and an increased sensitivity of bronchopulmonary C-fiber afferent endings may be involved. The present study was aimed at determining the effect of O3 on the responses of pulmonary C fibers to chemical and mechanical stimuli. A total of 31 C fibers were studied in anesthetized, open-chest, and vagotomized rats. During control, right atrial injection of a low dose of capsaicin abruptly evoked a short and mild burst of discharge [0.77 ± 0.28 impulses (imp)/s, 2-s average]. After acute exposure to O3 (3 parts/million for 30 min), there was no significant change in arterial blood pressure, tracheal pressure, or baseline activity of C fibers. However, the stimulatory effect of the same dose of capsaicin on these fibers was markedly enhanced (6.05 ± 0.88 impulses/s; P < 0.01) and prolonged immediately after O3 exposure, and returned toward control in 54 ± 6 min. Similarly, the pulmonary C-fiber response to injection of a low dose of lactic acid was also elevated after O3 exposure. Furthermore, O3 exposure significantly potentiated the C-fiber response to constant-pressure (tracheal pressure = 30 cmH2O) lung inflation (control: 0.19 ± 0.07 imp/s; after O3: 1.12 ± 0.26 imp/s; P < 0.01). In summary, these results show that the excitabilities of pulmonary C-fiber afferents to lung inflation and injections of chemical stimulants are markedly potentiated after acute exposure to O3, suggesting a possible involvement of these afferents in the O3-induced changes in breathing pattern and chest discomfort in humans.

Alveolar hypercapnia augments pulmonary C-fiber responses to chemical stimulants: role of hydrogen ion

2002 ◽  
Vol 93 (1) ◽  
pp. 181-188 ◽  
Author(s):  
Qihai Gu ◽  
Lu-Yuan Lee
Keyword(s):  
Hydrogen Ion ◽  
Right Atrial ◽  
Mechanical Stimuli ◽  
Hydrogen Ions ◽  
Lung Inflation ◽  
C Fibers ◽  
Arterial Blood ◽  
Blood Ph ◽  
C Fiber

To determine whether the excitabilities of pulmonary C fibers to chemical and mechanical stimuli are altered by CO2-induced acidosis, single-unit pulmonary C-fiber activity was recorded in anesthetized, open-chest rats. Transient alveolar hypercapnia (HPC) was induced by administering CO2-enriched gas mixture (15% CO2, balance air) via the respirator inlet for 30 s, which rapidly lowered the arterial blood pH from a baseline of 7.40 ± 0.01 to 7.17 ± 0.02. Alveolar HPC markedly increased the responses of these C-fiber afferents to several chemical stimulants. For example, the C-fiber response to right atrial injection of the same dose of capsaicin (0.25–1.0 μg/kg) was significantly increased from 3.07 ± 0.70 impulses/s at control to 8.48 ± 1.52 impulses/s during HPC ( n = 27; P < 0.05), and this enhanced response returned to control within ∼10 min after termination of HPC. Similarly, alveolar HPC also induced significant increases in the C-fiber responses to right atrial injections of phenylbiguanide (4–8 μg/kg) and adenosine (0.2 mg/kg). In contrast, HPC did not change the response of pulmonary C fibers to lung inflation. Furthermore, the peak response of these C fibers to capsaicin during HPC was greatly attenuated when the HPC-induced acidosis was buffered by infusion of bicarbonate (1.36–1.82 mmol · kg−1 · min−1 for 35 s). In conclusion, alveolar HPC augments the responses of these afferents to various chemical stimulants, and this potentiating effect of CO2 is mediated through the action of hydrogen ions on the C-fiber sensory terminals.

Selected Contribution: Hypersensitivity of pulmonary C fibers induced by adenosine in anesthetized rats

2003 ◽  
Vol 95 (3) ◽  
pp. 1315-1324 ◽  
Author(s):  
Qihai Gu ◽  
Ting Ruan ◽  
Ju-Lun Hong ◽  
Nausherwan Burki ◽  
Lu-Yuan Lee
Keyword(s):  
Receptor Antagonist ◽  
Potential Role ◽  
Right Atrial ◽  
Adenosine Infusion ◽  
Lung Inflation ◽  
C Fibers ◽  
Baseline Activity ◽  
Tracheal Pressure ◽  
C Fiber

Compelling clinical evidence implicates the potential role of adenosine in development of airway hyperresponsiveness and suggests involvement of pulmonary sensory receptors. This study was carried out to determine the effect of a low dose of adenosine infusion on sensitivity of pulmonary C-fiber afferents in anesthetized open-chest rats. Infusion of adenosine (40 μg · kg-1 · min-1 iv for 90 s) mildly elevated baseline activity of pulmonary C fibers. However, during adenosine infusion, pulmonary C-fiber responses to chemical stimulants and lung inflation (30 cmH2O tracheal pressure) were markedly potentiated; e.g., the response to right atrial injection of capsaicin (0.25 or 0.5 μg/kg) was increased by more than fivefold (change in fiber activity = 2.64 ± 0.67 and 16.27 ± 3.11 impulses/s at control and during adenosine infusion, n = 13, P < 0.05), and this enhanced response returned to control in ∼10 min. The potentiating effect of adenosine infusion was completely blocked by pretreatment with 8-cyclopentyl-1,3-dipropylxanthine (100 μg/kg), a selective antagonist of the adenosine A1 receptor, but was not affected by 3,7-dimethyl-1-propargylxanthine (1 mg/kg), an A2-receptor antagonist, or 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (2 mg/kg), an A3-receptor antagonist. This potentiating effect was also mimicked by N6-cyclopentyladenosine (0.25 μg·kg-1·min-1 for 90 s), a selective agonist of the adenosine A1 receptor. In conclusion, our results showed that infusion of adenosine significantly elevated the sensitivity of pulmonary C-fiber afferents in rat lungs and that this potentiating effect is likely mediated through activation of the adenosine A1 receptor.

Chronic exposure to sidestream tobacco smoke augments lung C-fiber responsiveness in young guinea pigs

1999 ◽  
Vol 87 (2) ◽  
pp. 757-768 ◽  
Author(s):  
T. Mutoh ◽  
A. C. Bonham ◽  
K. S. Kott ◽  
J. P. Joad
Keyword(s):  
Tobacco Smoke ◽  
Guinea Pigs ◽  
Chronic Exposure ◽  
Dynamic Compliance ◽  
Mechanical Stimuli ◽  
C Fibers ◽  
Arterial Blood ◽  
Baseline Activity ◽  
Tracheal Pressure ◽  
C Fiber

Children chronically exposed to environmental tobacco smoke (ETS) have more coughs, wheezes, and airway obstruction, which may result in part from stimulation of lung C fibers. We examined the effect of chronic exposure to sidestream tobacco smoke (SS, a surrogate for ETS) on lung C-fiber responsiveness in guinea pigs, in which dynamic compliance (Cdyn), lung resistance, tracheal pressure, arterial blood pressure, and heart rate were also monitored. Guinea pigs were exposed to SS (1 mg/mm3 total suspended particulates) or filtered air 5 days/wk from 1 to 6 wk of age. They were then anesthetized, and lung C fibers ( n = 55), identified by a conduction velocity of <2.0 m/s, were tested for responsiveness to chemical and mechanical stimuli. SS exposure doubled C-fiber responsiveness to left atrial capsaicin ( P = 0.02) and lung hyperinflation ( P = 0.03) but had no effect on responsiveness to inhaled capsaicin or bradykinin or on baseline activity. The data indicate that chronically exposing young guinea pigs to SS enhances C-fiber sensitivity to certain stimuli and may help explain respiratory symptoms in children exposed to ETS.

scholarly journals Effects of human eosinophil granule-derived cationic proteins on C-fiber afferents in the rat lung

2001 ◽  
Vol 91 (3) ◽  
pp. 1318-1326 ◽  
Author(s):  
Lu-Yuan Lee ◽  
Qihai Gu ◽  
Gerald J. Gleich
Keyword(s):  
Eosinophil Cationic Protein ◽  
Eosinophil Infiltration ◽  
Cationic Protein ◽  
Human Eosinophil ◽  
Lung Inflation ◽  
Cationic Proteins ◽  
C Fibers ◽  
Arterial Blood ◽  
C Fiber ◽  
Eosinophil Granule

Experiments were performed to test the hypothesis that human eosinophil granule-derived cationic proteins stimulate vagal C-fiber afferents in the lungs and elicit pulmonary chemoreflex responses in anesthetized Sprague-Dawley rats. Intratracheal instillation of eosinophil cationic protein (ECP; 1–2 mg/ml, 0.1 ml) consistently induced an irregular breathing pattern, characterized by tachypnea (change in breathing frequency of 44.7%) and small unstable tidal volume (Vt). The tachypnea, accompanied by decreased heart rate and arterial blood pressure, started within 30 s after the delivery of ECP and lasted for >30 min. These ECP-induced cardiorespiratory responses were completely prevented by perineural capsaicin treatment of both cervical vagi, which selectively blocked C-fiber conduction, suggesting the involvement of these afferents. Indeed, direct recording of single-unit activities of pulmonary C-fibers further demonstrated that the same dose of ECP evoked a pronounced and sustained (>30-min) stimulatory effect on pulmonary C-fibers. Furthermore, the sensitivity of these afferents to lung inflation was also markedly elevated after the ECP instillation, whereas the vehicle of ECP administered in the same manner had no effect. Other types of eosinophil granule cationic proteins, such as major basic protein and eosinophil peroxidase, induced very similar respiratory and cardiovascular reflex responses. In conclusion, these results show that eosinophil granule-derived cationic proteins induce a distinct stimulatory effect on vagal pulmonary C-fiber endings, which may play an important role in the airway hyperresponsiveness associated with eosinophil infiltration in the airways.

scholarly journals Hypersensitivity of vagal pulmonary C-fibers induced by increasing airway temperature in ovalbumin-sensitized rats

2015 ◽  
Vol 309 (10) ◽  
pp. R1285-R1291
Author(s):  
Yu-Jung Lin ◽  
Ruei-Lung Lin ◽  
Mehdi Khosravi ◽  
Lu-Yuan Lee
Keyword(s):  
Steady State ◽  
Direct Evidence ◽  
Right Atrial ◽  
Brown Norway ◽  
C Fibers ◽  
Baseline Activity ◽  
C Fiber ◽  
Chemical Stimuli ◽  
Sensitizing Effect ◽  
Norway Rats

Our recent study has shown that hyperventilation of humidified warm air (HWA) triggered cough and reflex bronchoconstriction in patients with mild asthma. We suggested that a sensitizing effect on bronchopulmonary C-fibers by increasing airway temperature was involved, but direct evidence was lacking. This study was carried out to test the hypothesis that HWA enhances the pulmonary C-fiber sensitivity in Brown-Norway rats sensitized with ovalbumin (Ova). In anesthetized rats, isocapnic hyperventilation of HWA for 3 min rapidly elevated airway temperature to a steady state of 41.7°C. Immediately after the HWA challenge, the baseline fiber activity (FA) of pulmonary C-fibers was markedly elevated in sensitized rats, but not in control rats. Furthermore, the response of pulmonary C-fibers to right atrial injection of capsaicin in sensitized rats was significantly higher than control rats before the HWA challenge, and the response to capsaicin was further amplified after HWA in sensitized rats (ΔFA = 4.51 ± 1.02 imp/s before, and 9.26 ± 1.74 imp/s after the HWA challenge). A similar pattern of the HWA-induced potentiation of the FA response to phenylbiguanide, another chemical stimulant of C-fibers, was also found in sensitized rats. These results clearly demonstrated that increasing airway temperature significantly elevated both the baseline activity and responses to chemical stimuli of pulmonary C-fibers in Ova-sensitized rats. In conclusion, this study supports the hypothesis that the increased excitability of these afferents may have contributed to the cough and reflex bronchoconstriction evoked by hyperventilation of HWA in patients with asthma.

scholarly journals Sensitizing effects of chronic exposure and acute inhalation of ovalbumin aerosol on pulmonary C fibers in rats

2008 ◽  
Vol 105 (1) ◽  
pp. 128-138 ◽  
Author(s):  
Guangfan Zhang ◽  
Ruei-Lung Lin ◽  
Michelle E. Wiggers ◽  
Lu-Yuan Lee
Keyword(s):  
Right Atrial ◽  
Brown Norway ◽  
Lung Inflation ◽  
Inflammatory Reactions ◽  
C Fibers ◽  
C Fiber ◽  
Inhalation Challenge ◽  
Sensitizing Effect ◽  
And Control ◽  
Norway Rats

The effect of ovalbumin (Ova) sensitization on pulmonary C-fiber sensitivity was investigated. Brown-Norway rats were sensitized by intraperitoneal injection of Ova followed by aerosolized Ova three times per week for 3 wk. Control rats received the vehicle. At the end of the third week, single-unit fiber activities (FA) of pulmonary C fibers were recorded in anesthetized, artificially ventilated rats. Our results showed the following: 1) Ova sensitization induced airway inflammation (infiltration of eosinophils and neutrophils) and airway hyperresponsiveness in rats; 2) baseline FA in sensitized rats was significantly higher than that in control ones; 3) similarly, the pulmonary C-fiber response to right atrial injection of capsaicin was markedly higher in sensitized rats, which were significantly amplified after the acute Ova inhalation challenge; and 4) similar patterns, but smaller magnitudes of the differences in C-fiber responses to adenosine and lung inflation, were also found between sensitized and control rats. In conclusion, Ova sensitization elevated the baseline FA and excitability of pulmonary C fibers, and the hypersensitivity was further potentiated after the acute Ova inhalation challenge in sensitized rats. Chronic allergic inflammatory reactions in the airway probably contributed to the sensitizing effect on these lung afferents.

Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output

2000 ◽  
Vol 279 (4) ◽  
pp. R1215-R1223 ◽  
Author(s):  
T. Mutoh ◽  
A. C. Bonham ◽  
J. P. Joad
Keyword(s):  
Substance P ◽  
Solitary Tract ◽  
C Fibers ◽  
Arterial Blood ◽  
Tracheal Pressure ◽  
C Fiber ◽  
Before And After ◽  
Neurokinin 1 ◽  
Central Synapses ◽  
Nerve Discharge

Bronchopulmonary C fibers defend the lungs against injury from inhaled agents by a central nervous system reflex consisting of apnea, cough, bronchoconstriction, hypotension, and bradycardia. Glutamate is the putative neurotransmitter at the first central synapses in the nucleus of the solitary tract (NTS), but substance P, also released in the NTS, may modulate the transmission. To test the hypothesis that substance P in the NTS augments bronchopulmonary C fiber input and hence reflex output, we stimulated the C fibers with left atrial capsaicin (LA CAP) injections and compared the changes in phrenic nerve discharge, tracheal pressure (TP), arterial blood pressure (ABP), and heart rate (HR) in guinea pigs before and after substance P injections (200 μM, 25 nl) in the NTS. Substance P significantly augmented LA CAP-evoked increases in expiratory time by 10-fold and increases in TP and decreases in ABP and HR by threefold, effects prevented by neurokinin-1 (NK1) receptor antagonism. Thus substance P acting at NTS NK1 receptors can exaggerate bronchopulmonary C fiber reflex output. Because substance P synthesis in vagal airway C fibers may be enhanced in pathological conditions such as allergic asthma, the findings may help explain some of the associated respiratory symptoms including cough and bronchoconstriction.

scholarly journals Epinephrine enhances the sensitivity of rat vagal chemosensitive neurons: role of β3-adrenoceptor

2007 ◽  
Vol 102 (4) ◽  
pp. 1545-1555 ◽  
Author(s):  
Qihai Gu ◽  
You-Shuei Lin ◽  
Lu-Yuan Lee
Keyword(s):  
Right Atrial ◽  
Intracellular Camp ◽  
Lung Inflation ◽  
Adrenoceptor Antagonist ◽  
C Fibers ◽  
Baseline Activity ◽  
Adrenoceptor Agonist ◽  
Intracellular Ca ◽  
Sensitizing Effect ◽  
Ganglion Neurons

This study was carried out to determine whether epinephrine alters the sensitivity of rat vagal sensory neurons. In anesthetized rats, inhalation of epinephrine aerosol (1 and 5 mg/ml, 3 min) induced an elevated baseline activity of pulmonary C fibers and enhanced their responses to lung inflation (20 cmH2O, 10 s) and right atrial injection of capsaicin (0.5 μg/kg). In isolated rat nodose and jugular ganglion neurons, perfusion of epinephrine (3 μM, 5 min) alone did not produce any detectable change of the intracellular Ca2+ concentration. However, immediately after the pretreatment with epinephrine, the Ca2+ transients evoked by chemical stimulants (capsaicin, KCl, and ATP) were markedly potentiated; for example, capsaicin (50 nM, 15 s)-evoked Ca2+ transient was increased by 106% after epinephrine ( P < 0.05; n = 11). The effect of epinephrine was mimicked by either BRL 37344 (5 μM, 5 min) or ICI 215,001 (5 μM, 5 min), two selective β3-adrenoceptor agonists, and blocked by SR 59230A (5 μM, 10 min), a selective β3-adrenoceptor antagonist, whereas pretreatment with phenylephrine (α1-adenoceptor agonist), guanabenz (α2-adrenoceptor agonist), dobutamine (β1-adrenoceptor agonist), or salbutamol (β2-adrenoceptor agonist) had no significant effect on capsaicin-evoked Ca2+ transient. Furthermore, pretreatment with SQ 22536 (100–300 μM, 15 min), an adenylate cyclase inhibitor, and H89 (3 μM, 15 min), a PKA inhibitor, completely abolished the potentiating effect of epinephrine. Our results suggest that epinephrine enhances the excitability of rat vagal chemosensitive neurons. This sensitizing effect of epinephrine is likely mediated through the activation of β3-adrenoceptor and intracellular cAMP-PKA signaling cascade.

Pulmonary C-fiber stimulation by capsaicin evokes reflex cholinergic bronchial vasodilation in sheep

1992 ◽  
Vol 72 (2) ◽  
pp. 770-778 ◽  
Author(s):  
H. M. Coleridge ◽  
J. C. Coleridge ◽  
J. F. Green ◽  
G. H. Parsons
Keyword(s):  
Bronchial Artery ◽  
Systemic Arterial Pressure ◽  
Right Atrial ◽  
Adrenergic Blockade ◽  
C Fibers ◽  
Arterial Blood ◽  
C Fiber ◽  
The Common ◽  
Vagal Cooling ◽  
Fiber Stimulation

We investigated changes in bronchial blood flow (Qbr) associated with capsaicin-induced stimulation of pulmonary C-fibers in seven anesthetized and two unanesthetized sheep. A Doppler flow probe chronically implanted around the common bronchial artery provided a signal (delta F, kHz) linearly related to bronchial arterial blood velocity (Vbr, cm/s), which was proportional to Qbr. An index of bronchial vascular conductance (Cbr, in arbitrary units) was calculated as the ratio of Vbr to systemic arterial pressure (Pa). Right atrial injection of capsaicin evoked a prompt pulmonary chemoreflex (apnea, bradycardia, and hypotension), with immediate increases in Vbr (average +34%) and Cbr (+63%) that reached a maximum approximately 7 s after the injection. A second increase in Vbr, but not in Cbr, occurred approximately 12 s later, coinciding with an increase in Pa. Vagal cooling (0 degrees C) prevented the pulmonary chemoreflex; it also abolished the immediate increases in Vbr and Cbr in four of six sheep and substantially reduced them in two sheep; it did not affect the late increases in Vbr and Pa. Results after atropine indicated that the immediate increases in Vbr and Cbr were mainly cholinergic. In two sheep a small residual vasodilation survived combined cholinergic and adrenergic blockade and may have been due to peripheral release of neurokinins.

Pulmonary C-fibers reflexly increase secretion by tracheal submucosal glands in dogs

1985 ◽  
Vol 58 (3) ◽  
pp. 907-910 ◽  
Author(s):  
H. D. Schultz ◽  
A. M. Roberts ◽  
C. Bratcher ◽  
H. M. Coleridge ◽  
J. C. Coleridge ◽  
...  
Keyword(s):  
Gland Secretion ◽  
Right Atrial ◽  
Vagus Nerves ◽  
C Fibers ◽  
Airway Secretion ◽  
Submucosal Glands ◽  
C Fiber ◽  
Anesthetized Dogs ◽  
The Right ◽  
Stimulation Of

Stimulation of bronchial C-fibers evokes a reflex increase in secretion by tracheal submucosal glands, but the influence of pulmonary C-fibers on tracheal gland secretion is uncertain. In anesthetized dogs with open chests, we sprayed powdered tantalum on the exposed mucosa of a segment of the upper trachea to measure the rate of secretion by submucosal glands. Secretions from the gland ducts caused elevations (hillocks) in the tantalum layer. We counted hillocks at 10-s intervals for 60 s before and 60 s after we injected capsaicin (10–20 micrograms/kg) into the right atrium to stimulate pulmonary C-fiber endings. Right atrial injection of capsaicin increased the rate of hillock formation fourfold, but left atrial injection had no significant effect. The response was abolished by cutting the vagus nerves or cooling them to 0 degree C. We conclude that the reflex increase in tracheal submucosal gland secretion evoked by right atrial injection of capsaicin was initiated as capsaicin passed through the pulmonary vascular bed, and hence that pulmonary C-fibers, like bronchial C-fibers, reflexly increase airway secretion.

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