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.

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.

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.

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 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.

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.

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.

Leukotriene B4 decreases the mechanical and thermal thresholds of C-fiber nociceptors in the hairy skin of the rat

1988 ◽  
Vol 60 (2) ◽  
pp. 438-445 ◽  
Author(s):  
H. A. Martin ◽  
A. I. Basbaum ◽  
E. J. Goetzl ◽  
J. D. Levine
Keyword(s):  
Acetic Acid ◽  
Glacial Acetic Acid ◽  
Leukotriene B4 ◽  
Thermal Stimulation ◽  
Mechanical Stimuli ◽  
Noxious Heat ◽  
C Fibers ◽  
Mechanical Threshold ◽  
C Fiber ◽  
Heat Threshold

1. We have recently shown that leukotriene B4 (LTB4), a product of the 5-lipoxygenase pathway of arachidonic acid metabolism, sensitizes nociceptors to mechanical stimuli. The present study examined whether LTB4 also induces a heat sensitization of cutaneous C-fiber nociceptors. The C-fiber nociceptors studied had von Frey hair thresholds greater than 5 g and were characterized according to their responses to noxious heat and chemical stimuli, including glacial acetic acid, bradykinin, and capsaicin. Thirty-four of the C-fibers that were activated by intense thermal stimulation were also activated by topical application of glacial acetic acid. They were classified as C-polymodal nociceptors (2, 28). Those that were activated by intense mechanical and thermal stimulation, but were unresponsive to acid, were classified as C-mechanoheat nociceptors (27). 2. Ninety-four percent of C-polymodal nociceptors and 60% of C-mechanoheat nociceptors were sensitized by LTB4. All C-fiber nociceptors that showed a decrease of their heat threshold also had a decrease of their mechanical threshold. LTB4 (75 ng) lowered the average heat threshold from 45 degrees C to 35 degrees C and produced an average decrease in the mechanical threshold of 86%. 3. The magnitude of the LTB4-evoked decrease in thermal threshold was similar to that produced by 75 ng of prostaglandin E2 (PGE2). These data demonstrate that LTB4 sensitizes C-mechanoheat nociceptors to both mechanical and thermal stimuli. 4. We conclude that LTB4 may contribute to the component of hyperalgesia that is resistant to nonsteroidal anti-inflammatory agents.

scholarly journals Sympathetic afferents in the hypogastric nerve facilitate nociceptive bladder activity in cats

2019 ◽  
Vol 316 (4) ◽  
pp. F703-F711 ◽  
Author(s):  
Yan Zhang ◽  
Shun Li ◽  
Todd Yecies ◽  
Tara Morgan ◽  
Haotian Cai ◽  
...  
Keyword(s):  
Bladder Capacity ◽  
Saline Control ◽  
Pelvic Nerve ◽  
Analgesic Agent ◽  
Hypogastric Nerve ◽  
C Fibers ◽  
Pelvic Nerves ◽  
C Fiber ◽  
Bladder Activity

This study in α-chloralose-anesthetized cats revealed a role of hypogastric nerve afferent axons in nociceptive bladder activity induced by bladder irritation using 0.25% acetic acid (AA). In cats with intact hypogastric and pelvic nerves, AA irritation significantly ( P < 0.05) reduced bladder capacity to 45.0 ± 5.7% of the control capacity measured during a saline cystometrogram (CMG). In cats with the hypogastric nerves transected bilaterally, AA irritation also significantly ( P < 0.05) reduced bladder capacity, but the change was significantly smaller (capacity reduced to 71.5 ± 10.6% of saline control, P < 0.05) than that in cats with an intact hypogastric nerve. However, application of hypogastric nerve stimulation (HGNS: 20 Hz, 0.2 ms pulse width) to the central end of the transected nerves at an intensity (16 V) strong enough to activate C-fiber afferent axons facilitated the effect of AA irritation and further ( P < 0.05) reduced bladder capacity to 48.4 ± 7.4% of the saline control. This facilitation by HGNS was effective only at selected frequencies (1, 20, and 30 Hz) when the stimulation intensity was above the threshold for activating C-fibers. Tramadol (an analgesic agent) at 3 mg/kg iv completely blocked the nociceptive bladder activity and eliminated the facilitation by HGNS. HGNS did not alter non-nociceptive bladder activity induced by saline distention of the bladder. These results indicate that sympathetic afferents in the hypogastric nerve play an important role in the facilitation of the nociceptive bladder activity induced by bladder irritation that activates the silent C-fibers in the pelvic nerve.

Cerebrospinal fluid in man native to high altitude

1964 ◽  
Vol 19 (2) ◽  
pp. 319-321 ◽  
Author(s):  
J. W. Severinghaus ◽  
A. Carceleń B.
Keyword(s):  
Cerebrospinal Fluid ◽  
High Altitude ◽  
Sea Level ◽  
Regulation Of Respiration ◽  
Acid Base ◽  
Peripheral Chemoreceptor ◽  
Arterial Blood ◽  
Blood Ph ◽  
The Difference

CSF pH was shown in a prior report to remain essentially constant during 8 days of acclimatization to 3,800 m. In order to further evaluate the possible role of CSF acid-base equilibria in the regulation of respiration, 20 Peruvian Andean natives were studied at altitudes of 3,720–4,820 m. In ten subjects at 3,720 m, means were: CSF pH 7.327, Pco2 43, HCO3- 21.5, Na+ 136, K+ 2.6, Cl- 124, lactate 30 mg/100 ml. Arterial blood: pH 7.43, Pco2 32.5, HCO3- 21.3, Na+ 136, K+ 4.2, Cl- 107, hematocrit 49, SaOO2 89.6. In six subjects at 4,545 m and four at 4,820 m CSF values were not significantly different; mean arterial Pco2 was 32.6 and 32.3, respectively. The only significant variations with altitude were the expected lowering of PaOO2 to 47 and 43.5 mm Hg, and of SaOO2 to 84.2 and 80.7, and increase of hematocrit to 67% and 75%, respectively. The natives differed from recently acclimatized sea-level residents in showing less ventilation (higher Pco2) in response to the existing hypoxia, and less alkaline arterial blood. The difference appears to relate to peripheral chemoreceptor response to hypoxia rather than central medullary chemoreceptor. respiratory regulation at high altitude; chronic acclimatization to altitude; peripheral chemoreceptor response to hypoxia; CSF and medullary respiratory chemoreceptors Submitted on June 12, 1963

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